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Biomedical subjects

L Palmer

Publications and source records attributed to L Palmer.

At least 19 recordsLinked to original sources

Contextual control of conflicting associations in the developing rat.

Two experiments examined the effects of manipulations of contextual cues on the expression of conflicting associations in 18-, 26-, and 35-day-old rats. Subjects learned to GO RIGHT in a water-filled T-maze, then were trained to reverse this position habit (GO LEFT). When the competing responses were learned in the same visual context, all age groups displayed a recency effect on a subsequent test in extinction; they behaved in accordance with the last-learned GO LEFT habit. If the competing responses were learned in different visual contexts, and testing took place in the context of the first problem, 35-day-old subjects behaved in a manner consistent with the GO RIGHT context (reduced recency). However, similarly trained 18-day-old subjects showed no evidence of a reduced recency effect. Given that 18-day-old rats are sensitive to other context manipulations, the present results suggest that the ability to "disambiguate" conflicting associations by context may depend upon the maturation of a relatively late-developing configural learning system.

Animals

Simple discrimination isn't really simple. A confirmatory analysis of the Speech Sound Pattern Discrimination Test.

This paper reports the results of a componential analysis of items comprising the Speech Sound Pattern Discrimination Test (SSPDT). The SSPDT, developed by Bochner et al. (1986), uses a closed-set sentence discrimination task to assess the auditory speech processing skill of severely and profoundly hearing-impaired individuals. A set of components reflecting differences in the phonetic and task-related characteristics of the test stimuli was developed, and the contributions of the components to discrimination task difficulty were evaluated using linear regression methodology. Discrimination task difficulty indices were transformations of percent-correct scores, resulting from fit of the SSPDT data to the Rasch measurement model. Three of the hypothesized components (one spectral, one temporal, and one task-related) entered a stepwise regression solution. These components have an intrinsic role in the construct validity of the instrument. The structure of the discrimination task, however, is more complex than might be suspected, because 'same' or matching test stimuli showed advantages in ease of discriminability compared with their 'different' or non-matching counterparts. The study findings will facilitate development of an enlarged item bank, and aid in the interpretation of test scores.

Adult

Loss of heterozygosity and mitotic linkage maps in the mouse.

Loss of heterozygosity is a significant oncogenetic mechanism and can involve a variety of mechanisms including chromosome loss, deletion, and homologous interchromosomal mitotic recombination. Analysis of H-2 antigen-loss variants from heterozygous murine cell lines provides an experimental system to estimate the relative contributions of different mechanisms for allele loss and to compare the chromosomal patterns of mitotic and meiotic recombination. Cytotoxic anti-H-2D antibodies and complement were used to isolate 161 independent target antigen-negative clones from H-2d/H-2b heterozygous cell lines; of these, 131 (84.5%) lost the allele encoding the target antigen. Allele-loss variants were typed and scored as either heterozygous or homozygous for six H-2D-proximal chromosome 17 markers and for one distal marker by restriction enzyme-site variations and Southern analysis. A single mitotic crossover could account for 50 clones (37%), with heterozygosity for at least one proximal marker and loss of heterozygosity for all markers distal to the putative recombination site. Eighty-two allele-loss variants (60%) were homozygous for all markers; the origin of these clones could be either chromosome loss or mitotic recombination between the centromere and the most proximal marker. Only 4 clones (3%) arose through more complex events such as multiple crossovers or deletion. A mitotic linkage map for mouse chromosome 17 was constructed, and the gene order deduced from somatic recombination was identical to that obtained by conventional transmission genetics. These results demonstrate that mitotic recombination is a common event leading to allele loss, in spite of the lack of evidence for frequent somatic pairing of homologous chromosomes. Mitotic mapping provides a defined system for comparison of mitotic and meiotic recombination and may lead to practical advances for elucidating somatic mechanisms of oncogenesis and for gene therapy in targeting mutations to specific sites through homologous recombination.

Alleles

Epidural sufentanil for post-caesarean section analgesia: lack of benefit of epinephrine.

Epidural sufentanil was administered to 57 women after Caesarean section, under epidural anaesthesia, to provide postoperative analgesia. Each patient received a 30 micrograms dose at the first complaint of pain and this dose was repeated when pain recurred. Epinephrine (1:200,000) was added to the local anaesthetic, sufentanil, both, or neither. The time of onset of analgesia, efficacy, duration of analgesia and the incidence of side-effects were recorded. This dose of epidural sufentanil provided satisfactory postoperative analgesia and no serious side-effects were observed. The onset of analgesia was rapid (4-6 min), but the duration of action was brief (4-5 hr). The addition of 1:200,000 epinephrine had no statistically significant influence on any of the measured variables. Pruritus occurred commonly but never required treatment. Drowsiness was experienced frequently and was felt by some patients to inhibit their interaction with their neonates. Respiratory depression, as defined by a respiratory rate less than 10 bpm, was not observed. A number of patients noted a transient period of euphoria 5-8 min after administration of the epidural sufentanil. The authors feel that epidural sufentanil provides satisfactory analgesia after Caesarean section, but the brief duration of action and the high incidence of drowsiness limit its acceptability for routine use in obstetric patients.

Adult

Epidural morphine for analgesia after caesarean section: a report of 4880 patients.

This retrospective study was undertaken to assess the efficacy and safety of epidural morphine in providing analgesia following Caesarean section under epidural anaesthesia. The morphine was administered as a single bolus, following delivery, in doses ranging from 2 to 5 mg. The charts of 4880 Caesarean sections, performed on 4500 patients, were reviewed. The duration of analgesia and the occurrence of any symptoms which might be side-effects of the epidural morphine were recorded. The duration of analgesia was 22.9 +/- 10.1 hr and was not correlated with the dose of epidural morphine. Eleven per cent of the patients required no supplemental analgesia during the first 48 hr. Twelve patients (0.25 per cent) had respiratory rates less than 10 breaths per minute, on at least one occasion. No serious sequelae resulted from these periods of bradypnoea. Pruritus occurred in 58 per cent of patients, nausea and vomiting in 39.9 per cent and dizziness in ten per cent. Herpes simplex labialis was recorded in 3.5 per cent of patients. Epidural morphine is thus confirmed as an effective analgesic technique post-Caesarean section with 3 mg being the optimal dose. Even in this young healthy patient population, clinically detectable respiratory depression occurs so clinical respiratory monitoring is indicated.

Acetaminophen

Expression of gonococcal protein II in Escherichia coli by translational fusion.

A protein II (P.II) gene from Neisseria gonorrhoeae was cloned in Escherichia coli and characterized by DNA sequence analysis. As with other reported P.II sequences, this gene contains an ATG initiation codon which is out of frame with respect to the remainder of the P.II amino acid sequence. A translational fusion was constructed in E. coli which linked the P.II sequence to the signal peptide of beta-lactamase. This P.II fusion differs from the gonococcal protein only in the first seven residues at the N terminus. In E. coli, the P.II fusion product exhibits properties analogous to those of P.II in N. gonorrhoeae. The P.II fusion product is a major component of the E. coli outer membrane and it is exposed on the cell surface. The P.II fusion protein also exhibits the heat-modifiable phenotype of gonococcal P.II.

Amino Acid Sequence

Use of a Chlamydia trachomatis DNA probe for detection of ocular chlamydiae.

We examined the efficacy of a Chlamydia trachomatis DNA probe in detecting ocular chlamydiae by comparing it with tissue culture isolation, direct fluorescent-antibody cytology, and clinical eye exams. In a trachoma-endemic area of Nepal, 430 Nepalese villagers were examined according to the World Health Organization trachoma grading scale. Upper tarsal conjunctival specimens from each subject were obtained for DNA probing, tissue culture, and fluorescent-antibody screening. Moderate to severe intensity of inflammation was found in 85 (21%) of 430 people studied. An additional 25 (7.2%) of 345 people with low or no intensity of inflammation also had microbiologically proven infection, which may reflect asymptomatic carriage. Compared with culture, the DNA probe had a sensitivity of 86.9% and a specificity of 91%. For direct fluorescent antibody versus culture, the values were 47.8 and 96.9%, respectively. Results from this study indicate that the DNA probe for C. trachomatis might be considered a valuable epidemiologic tool in screening trachoma-endemic populations for ocular chlamydiae.

Adolescent

A comparative study of patient controlled epidural analgesia (PCEA) and continuous infusion epidural analgesia (CIEA) during labour.

In a randomised, single-blinded, placebo-controlled study, 27 parturients in labour receiving epidural 0.125 per cent bupivacaine, were assessed to evaluate the efficacy of patient-controlled epidural analgesia (PCEA) compared with continuous infusion epidural analgesia (CIEA). Group A (n = 14) received a background infusion of 4 ml.hr-1 0.125 per cent bupivacaine, with further 4 ml aliquots, self-administered, as required (up to 16 ml.hr-1). Group B (n = 11) received a continuous infusion of 12 ml.hr-1 through the same PCA apparatus, but with the demand-button deactivated. Both groups were similar in respect to age, height, weight, duration and outcome of labour, birthweight and neonatal Apgar scores. Patients in Group A (PCEA) received significantly less local anaesthetic than those in Group B (11.2 vs 15.2 mg.hr-1). Pain relief was similar in both groups. Patients expressed overall satisfaction with PCEA, appreciating control over their own pain relief and less reliance on medical staff. PCEA is a safe, effective means of providing optimal analgesia during labour, with minimal local anaesthetic requirement.

Adult

Sodium transport in a mouse model of colonic carcinogenesis.

Following 4 weeks of s.c. injections of 1,2-dimethylhydrazine, a carcinogen that produces colon cancer in CF1 mice, an increase in the unidirectional mucosal to serosal flux and net absorption of sodium was observed in the distal colon. This increase in sodium transport was amiloride sensitive. 1,2-Dimethylhydrazine treatment had no effect on sodium transport in the distal colon of DBA/2 mice, a strain which does not develop colonic malignant transformation. Although stimulation of sodium transport has been observed in cultured cell systems exposed to growth factors, similar changes in sodium transport have not previously been demonstrated in an intact epithelium at an early stage of carcinogenesis. The present study in mouse distal colon demonstrates that sodium transport is altered in 1,2-dimethylhydrazine-induced malignant transformation of the large bowel.

1,2-Dimethylhydrazine

T4 lymphopenia in human tuberculosis.

Lymphocyte subpopulations in vitro in 13 patients with bacteriologically-proven tuberculosis and 12 matched controls, by immunofluorescence using monoclonal antibodies have been studied. Active tuberculosis was associated with significant reductions in absolute numbers of total T (Leu 4 or 1+), T4 (Leu 3a+) and B (Leu 12+) lymphocytes, but there were no significant differences in total T8 (Leu 2a+) counts. In two patients, T4-lymphopenia was sufficiently profound to cause reversal of T4: T8 ratio (less than 1.2). These changes were not related to the radiological extent of the disease or size of the Mantoux reaction. Normal ranges for the different classes of lymphocytes were readily restored by chemotherapy.

B-Lymphocytes

Chronic beryllium disease in a precious metal refinery. Clinical epidemiologic and immunologic evidence for continuing risk from exposure to low level beryllium fume.

Five workers at a precious metal refinery developed granulomatous lung disease between 1972 and 1985. The original diagnosis was sarcoidosis, but 4 of the workers were subsequently proved to have hypersensitivity to beryllium by in vitro proliferative responses of lymphocytes obtained by bronchoalveolar lavage. Review of medical records of coworkers and extensive industrial hygiene surveillance of the plant demonstrated that 4 cases occurred in the furnace area where air concentrations of beryllium fume were consistently below the permissible exposure limit of 2 micrograms/M3. A single case has been recognized from parts of the refinery where exposures to cold beryllium dust often exceeded the standard by as much as 20-fold. These data demonstrate that chronic beryllium disease still occurs and confirm the importance of specific immunologic testing in patients suspected of having sarcoidosis but with potential exposure to beryllium. The data raise concern about the adequacy of modern industrial controls, especially in the setting of exposure to highly respirable beryllium fume.

Adult

Regulation of accessory cell function by retinoids in murine immune responses.

This study examines the effects of in-vivo immune regulation by vitamin A acetate (VAA) and 13-cis-retinoic acid (13-CRA) on in-vitro accessory cell function. Mice were fed a control diet, or diet containing VAA or 13-CRA, and monitored by body weight gains and diet consumptions at weekly intervals. At 4, 7 and 12 weeks mice were killed, differential blood counts performed and accessory cells isolated from lymphomedullary tissues. Histology confirmed that the chief feature of the lymphomedullary organs of the VAA-fed animals was an expansion of the splenic marginal zone and the paracortical region of the lymph nodes. There was an increase in the number of accessory cells present, and this included both dendritic cells and macrophages. The accessory cell function of these cells was also increased, as evidenced by both alloproliferative and allocytotoxic responses in vitro. In 13-CRA-fed animals the effects were similar to those seen with VAA, but were less pronounced. We suggest that the primary effects of these compounds on in-vivo immunoregulation could be due to their promotion of accessory cell function.

Animals

A common plasmid of Chlamydia trachomatis.

A 7.4-kb plasmid is a common and perhaps essential component of the Chlamydia trachomatis genome. This plasmid occurs as 10 copies per chlamydial chromosomal equivalent. It is unable to replicate in Escherichia coli. Complete plasmid genomes from eight serovars of C. trachomatis have been isolated in E. coli as cloned sequences ligated to pBR322. Restriction enzyme cleavage site mapping indicates that these plasmids are closely related. Homologous plasmid sequences have also been detected by DNA hybridization in all of the 200 clinically isolated strains of C. trachomatis which have been examined. DNA sequences homologous to the C. trachomatis plasmid were not found in eucaryotic DNA nor in a plasmid of similar size isolated from C. psittaci. C. trachomatis plasmid genes are expressed in vivo and the plasmid encoded gene products may play a role in the intracellular growth of this organism. Plasmid encoded genes were also expressed from the cloned C. trachomatis plasmid in E. coli minicells and using an E. coli S-30 in vitro transcription translation extract.

Chlamydia trachomatis

Use of nucleic acid probes for the detection of sexually transmitted infectious agents.

Deoxyribonucleic acid sequences specific for a pathogen of interest can be isolated from a variety of microorganisms. Such DNA probes can be exploited to detect infectious agents directly in infected patient material despite the presence of large numbers of other organisms and host DNA. This technology is dependent upon the recognition of a specific nucleotide sequence present in DNA extracted from a clinical sample by a radiolabeled or nonisotopically labeled DNA probe. We have isolated several DNA probes for the detection of pathogenic Neisseria which include a plasmid species unique to the gonococcus, as well as several cloned genes that detect both the gonococcus and the meningococcus. In addition, we characterized a unique plasmid of Chlamydia trachomatis that has proved to be quite useful as a DNA probe for the detection of this pathogen in cervical secretions and, by in situ hybridization, in Papanicolaou smears. Deoxyribonucleic acid hybridization as a diagnostic tool is still in its infancy. It holds a number of advantages over conventional methods of pathogen detection and serves as an alternative, as well as a complement, to available immunologic methods.

Bacterial Outer Membrane Proteins

A closed-set sentence protocol for assessing speech discrimination in deaf individuals: the speech sound pattern discrimination test.

Forty hearing-impaired young adults were tested with a newly developed instrument designed to assess auditory speech processing skill. Analyses indicated that the resulting test data could be characterized in terms of the Rasch model for person measurement. Evidence of the scale's empirical validity also was obtained. The instrument uses a closed-set sentence discrimination task, and appears to be useful over a fairly wide range of hearing losses.

Adult

Error propagation in viable cells.

Error propagation is the process, predicted by theoretical models, whereby errors in translating the genetic code will beget fresh errors in successive generations. It has been postulated that error propagation may underly the mortality of cells which display clonal senescence. We have demonstrated the occurrence of error propagation in viable cells of E. coli during growth in a low concentration of streptomycin, a drug which promotes ribosomal ambiguity. We monitored error propagation by measuring mistranslation of a specific UAA codon, and measured viability by direct enumeration of both live and dead cells through a sensitive microscopic technique. We find that the error frequency may be artificially increased by at least an order of magnitude without generating any detectable increase in the proportion of dead cells or of cells whose descendents are doomed to clonal senescence. The error frequency increases gradually over the course of a few generations, in qualitative agreement with the notion of error propagation, and eventually stabilizes at a constant value much higher than normal. The kinetics of this increase agree quantitatively with the Hoffman-Kirkwood and Holliday formulation of error propagation, for parameter values which dictate convergence to a stable error frequency. This convergent behaviour, under conditions of enhanced mistranslation, demonstrates that the normal parameters are well removed from the region of instability in error propagation; even an order of magnitude increase in mistranslation does not tip the translation system into the unstable mode which has been postulated to underly cell senescence. Thus, the error catastrophe theory of cell senescence cannot apply to the translation system of bacteria. We have reviewed experimental data on the fidelity of translation in somatic cells of higher organisms which militate against the notion that the translation system in these cell types could be much closer to the region of instability than in bacteria. These considerations controvert the error catastrophe theory of cell senescence.

Alkaline Phosphatase

Regulatory nucleotides involved in the Rel function of Bacillus subtilis.

We have examined the accumulation of polyphosphorylated nucleotides in Bacillus subtilis in relation to the function of the rel gene. Our results are as follows. (i) During inhibition of isoleucine activation by O-methylthreonine, wildtype B. subtilis cells accumulate unusual nucleotides with the chromatographic and chemical properties of pppApp, ppApp, pppGpp, ppGpp, pGpp, and ppGp. (ii) During the carbon source downshift elicited by inhibiting glucose uptake, we observed accumulation of the polyphosphorylated guanosine but not adenosine nucleotides. (iii) At the end of long phase in sporulation medium, we observed a small transient accumulation of the polyphosphorylated guanosine but not adenosine nucleotides. (iv) We were unable to detect a nucleotide with chromatographic behavior expected for pppAppp under any conditions. (v) The rel mutant of Swanton and Edlin (Biochem. Biophys. Res. Commun. 46-583-588, 1972) did not accumulate any of these polyphosphorylated nucleotides under any of the conditions examined. (vi) the rel mutant is unimpaired in sporulation. We conclude that one or more of the nucleotides we have detected may be involved in controlling the specificity of transcription during the stringent response, but none of them are required for sporogenesis.

Adenine Nucleotides