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Biomedical subjects

S Kemp

Publications and source records attributed to S Kemp.

At least 55 records · Page 3Linked to original sources
PubMed1996

Association as a cause of dating bias.

Two experiments investigated a dating bias in which people tend to estimate recent dates too remotely and remote dates too recently. Experiment 1 examined and upheld a prediction of the hypothesis that bias arises because events whose time of occurrence is unknown are dated through associated events for which some time information is available. Experiment 2 required some subjects to date prototype events while others dated specific events. Prototype events were dated more recently, and the errors in dating specific events were related to differences in the way the prototype events were dated. Both sets of results were predicted by the association hypothesis, according to which events whose dates are well known are dated with reference either to specific associated events or to prototype events.

Adult↗
PubMed1995

Anger theory and management: a historical analysis.

Ancient and medieval views on anger--its desirability, causes, and control--are reviewed and compared with modern accounts. Although some differences emerge, for example with respect to women's anger, the modern accounts bear a marked resemblance to the older ones. There is also an early concern with the practice of anger management.

Adaptation, Psychological↗
PubMed1995

Spectrum of mutations in the gene encoding the adrenoleukodystrophy protein.

X-linked adrenoleukodystrophy (ALD) has been associated with mutations in a gene encoding an ATP-binding transporter, which is located in the peroxisomal membrane. Deficiency of the gene leads to impaired peroxisomal beta-oxidation. Systematic analysis of the open reading frame of the ALD gene, using reverse transcriptase-PCR, followed by direct sequencing, revealed mutations in all 28 unrelated kindreds analyzed. No entire gene deletions or drastic promoter mutations were detected. In only one kindred did the mutation involve multiple exons. The other mutations were small alterations leading to missense (13 of 28) or nonsense mutations, a single amino acid deletion, frameshifts, or splice acceptor-site defects. Mutations affecting a single amino acid were concentrated in the region between the third and fourth putative transmembrane domains and in the ATP-binding domain. Mutations were detected in all investigated ALD kindreds, suggesting that this gene is the only gene responsible for X-linked ALD. This overview of mutations is useful in the determination of structurally and functionally important regions and provides an efficient screening strategy for identification of mutations in the ALD gene.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1994

Identification of a two base pair deletion in five unrelated families with adrenoleukodystrophy: a possible hot spot for mutations.

The gene for X-linked adrenoleukodystrophy (ALD) was recently identified. Intragenic deletions of several kilobases were found in about 7% of patients. Point mutations, expected to be very heterogeneous, were identified so far in only two patients. We report the identification of a two base pair deletion at position 1801-1802 of the ALD cDNA, located within the fifth exon of the ALD gene, which precedes the two consensus motives for ATP-binding. This microdeletion was found in five out of 40 unrelated ALD kindreds, indicating that this position is a hot spot for mutations. The mutation was observed both in patients with childhood cerebral ALD (CCALD) and in patients with adrenomyeloneuropathy (AMN).

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1993

N-glycosylation and deletion mutants of the human MDR1 P-glycoprotein.

P-glycoproteins are heavily glycosylated plasma membrane proteins, which confer multidrug resistance by pumping a range of different drugs from the cell. To investigate the significance of the conserved N-glycosylation sites present in the putative first extracellular loop of P-glycoproteins, we mutated one, two, or all three of these sites present in the human MDR1 P-glycoprotein. We also deleted a stretch of 20 amino acids, containing two of the three N-glycosylation sites. The effects of these mutations were studied by transfection into drug-sensitive cells. In vincristine-resistant transfected clones selected for similar steady state levels of membrane-bound P-glycoprotein, the absence of N-glycosylation did not alter the level or pattern of (cross-)resistance. However, the absence of N-glycosylation sites drastically reduced the efficiency with which drug-resistant clones could be generated. These findings suggest that N-glycosylation contributes to proper routing or stability of P-glycoprotein but not to drug transport per se. The deletion mutants demonstrated a clearly decreased and altered drug resistance pattern, even with a high level of P-glycoprotein in the plasma membrane. This, and possibly the observed lack of glycosylation of the remaining intact glycosylation sequence, suggests a constrained P-glycoprotein structure. Our findings support the current model for P-glycoprotein structure.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Deletion of the serine 34 codon from the major peripheral myelin protein P0 gene in Charcot-Marie-Tooth disease type 1B.

Charcot-Marie-Tooth disease type 1B (CMT1B) is genetically linked to chromosome 1q21-23. The major peripheral myelin protein gene, P0, has been cloned and localized to the same chromosomal region. P0 is a 28 kDa glycoprotein involved in the compaction of the multilamellar myelin sheet and accounts for more than half of the peripheral myelin protein content. We checked whether P0 is altered in CMT1B, and show here that a 3 basepair deletion in exon 2 of the P0 gene is present in all affected individuals of a CMT1B family. The mutation results in the deletion of serine 34 in the extracellular domain of P0, suggesting that alterations of P0 cause CMT1B.

Amino Acid Sequence↗
PubMed1993

Recognition and recall of visual area.

When visual areas are recalled the ratio of two areas is compressed relative to both the actual and perceived values (e.g. Kemp, 1988). Experiment 1 replicated this effect with a simple two-region figure, and Expt 2 showed a significant increase in area compression to occur between 2 min and 1 week when subjects were asked to recognize the two-region figure from a set of nine figures with different area ratios. Area compression was also found in Expt 3 where a different figure was used. Experiment 4 found that varying the texture of the smaller region of a two-region figure had no significant effect on area compression, and in Expt 5 subjects choose a figure in which the area was expanded but the texture was unchanged over one in which the texture was expanded with the area. Experiment 6 showed that compression of remembered areas seen in a photograph did not depend on recalled distance. In conclusion, area compression appears to arise from a gradual transformation of remembered area that does not resemble a zooming process.

Humans↗
PubMed1992

Masking of tinnitus induced by sound.

Two experiments were performed in which 8 listeners used external sound to mask the tinnitus induced by a 95-dB SPL tone presented for 1 min. Wider bandwidth noises were more effective maskers than noises of critical bandwidth, which, in turn, were more effective than tonal maskers. Contralateral maskers were often effective, but less so than ipsilateral maskers. Tuning curves showed some degree of frequency specificity that was not related to the frequency of the tinnitus-inducing tone. There were consistent and pronounced differences between individual listeners. Overall, our results indicate both similarities and differences between the masking of induced tinnitus and the masking of pathological tinnitus.

Adult↗
PubMed1992

Diaries of tinnitus sufferers.

Nine tinnitus sufferers kept daily diaries of their tinnitus experiences for up to three months. Levels of the loudest and quietest tinnitus and tinnitus annoyance were moderately highly correlated with each other and weakly correlated with the degree of sleep disturbance. Fluctuations in tinnitus sensation were frequent and associated with higher perceived levels and annoyance. Results were complicated by individual differences in tinnitus and lifestyle.

Adult↗
PubMed1991

A survey of New Zealanders with tinnitus.

A sample of 338 New Zealanders regularly experiencing tinnitus completed questionnaires posted to associations for people with tinnitus or hearing impairment. Nearly half the sample was sometimes depressed by tinnitus; those reporting depression and those reporting more severe problems as a consequence of their tinnitus saw more health-care professionals and used more coping strategies. Most respondents did not remember exactly when they first noticed their tinnitus; those that did reported a range of events that might have precipitated it. Respondents who sought medical help generally rated professionals as sympathetic, but few had been offered effective treatment. Comparison of the tinnitus sample with a sample of university students and staff indicated that though the respondents of the university sample often had some experience of tinnitus they reported sensations rather different from those of the tinnitus sample.

Adaptation, Psychological↗
PubMed1991

Retrospective duration estimation of public events.

In three experiments, we investigated subjects' retrospective estimation of the duration of publicly reported events such as, for example, the Falkland's war. In Experiment 1, duration estimates were found to be positively correlated with event knowledge, in keeping with Ornstein's (1969) model of duration estimation. Event duration was, however, generally underestimated, suggesting that the relationship between event knowledge and estimated duration might reflect an increase in estimation accuracy. Other results of Experiment 1 were consistent with this interpretation and suggested that the duration estimates might be largely reconstructed. In Experiment 2, duration estimates of specific events and general categories of events were found to be highly correlated, and the subjects in Experiment 3 indicated that they used knowledge of the general characteristic of different types of events to estimate event duration. Overall, reallife duration estimates appear to be based on a combination of specific event information and knowledge derived about that category of event.

Adult↗
PubMed1989

Investigation of tinnitus induced by sound and its relationship to ongoing tinnitus.

Tinnitus was temporarily induced by monaurally presented sound, and its level monitored using a dichotic loudness-matching task. The first experiment found no effect of varying the level, bandwidth, or center frequency of an inducing noise on the level or duration of the induced tinnitus; nor was there any difference when tones or different noises were used to induce tinnitus. The rated loudness of the tinnitus, however, increased with the level and decreased with the center frequency of the noise. The second experiment investigated tinnitus induced by a 1-kHz, 95-dB SPL tone in 53 subjects with thresholds in the normal range, but with varying degrees of ongoing tinnitus that ranged from no discernible sound sensation at all, through an apparently normal but usually inaudible noise or ringing, to constant or near-constant tinnitus. Individual differences in induced tinnitus were found that were related to differences in ongoing tinnitus; for example, the levels of induced and ongoing tinnitus were positively correlated. The results suggest that some kinds of ongoing tinnitus may arise from the auditory process responsible for induced tinnitus.

Adolescent↗
PubMed1989

Structural characterization of HIV reverse transcriptase: a target for the design of specific virus inhibitors.

The reverse transcriptase (RT) of HIV is an important target for chemotherapy as demonstrated by the effective treatment of AIDS patients with zidovudine, a potent inhibitor of RT. Structural studies of HIV RT were therefore undertaken with a view to designing more effective inhibitors. To obtain sufficient quantities of enzyme for these studies the reverse transcriptase gene of HIV was cloned into a high level expression plasmid yielding reverse transcriptase at a level of 10% of the total Escherichia coli proteins. Monoclonal antibodies to RT were raised in mice and have been used to purify the enzyme by immunoaffinity chromatography. Crystallization of the enzyme has been achieved and studies are underway to determine its three-dimensional structure. In addition, carboxy-terminal truncated mutants were prepared by inserting stop codons into the gene at appropriate sites. The proteins expressed were analysed for RT and RNase H activity and used for mapping RT epitopes. This, together with previous data on site-directed mutagenesis of conserved regions of HIV RT has helped to map some of the structural and functional regions of the enzyme.

Animals↗
PubMed1989

Characterization of a DNA polymerase mutant of herpes simplex virus from a severely immunocompromised patient receiving acyclovir.

A series of herpes simplex virus isolates were recovered from a bone marrow transplant patient who received prolonged acyclovir therapy for indolent herpes simplex mouth and throat ulceration. Of 14 isolates received 10 were resistant to acyclovir and partially resistant to phosphonoacetic acid. Biochemical characterization revealed that resistance was due to an alteration in the virus DNA polymerase. DNA sequence analysis of the polymerase gene of a plaque-purified resistant virus isolate revealed a single nucleotide change when compared with the sequence of the gene of a plaque-purified sensitive isolate. This single base change resulted in a predicted amino acid substitution of Gly to Ser at residue number 841, a putative functional region of the polymerase.

Acyclovir↗
PubMed1989

The role of herpes simplex virus type 1 thymidine kinase in pathogenesis.

A genetically engineered herpes simplex virus type 1 (HSV-1)thymidine kinase (TK) deletion mutant has been constructed and used to investigate the role of this gene in pathogenesis. Inoculation of mice with the HSV TK deletion mutant resulted in the establishment of latent ganglionic infection as demonstrated by superinfection of explanted ganglia with wild-type (wt) virus but not by routine explant culture suggesting that the virus-encoded TK is not essential for the establishment of latent infection but may be necessary for either reactivation or virus replication following reactivation. In addition, Southern blot hybridization has been used to demonstrate in vivo complementation of this mutant by wt virus in both peripheral and central nervous system tissues of mice during acute infection and to show that such complementation can result in the establishment and reactivation of latent TK- infection.

Acute Disease↗