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Biomedical subjects

P Clark

Publications and source records attributed to P Clark.

At least 163 records · Page 9Linked to original sources
PubMed1993

Growth cone guidance and neuron morphology on micropatterned laminin surfaces.

Neurite growth cones detect and respond to guidance cues in their local environment that determine stereotyped pathways during development and regeneration. Micropatterns of laminin (which was found to adsorb preferentially to photolithographically defined hydrophobic areas of micropatterns) were here used to model adhesive pathways that might influence neurite extension. The responses of growth cones were determined by the degree of guidance of neurite extension and also by examining growth cone morphology. These parameters were found to be strongly dependent on the geometry of the patterned laminin, and on neuron type. Decreasing the spacing of multiple parallel tracks of laminin alternating with non-adhesive tracks, resulted in decreased guidance of chick embryo brain neurons. Single isolated 2 microns tracks strongly guided neurite extension whereas 2 microns tracks forming a 4 microns period multiple parallel pattern did not. Growth cones appear to be capable of bridging the narrow non-adhesive tracks, rendering them insensitive to the smaller period multiple parallel adhesive patterns. These observations suggest that growth cones would be unresponsive to the multiple adhesive cues such as would be presented by oriented extracellular matrix or certain axon fascicle structures, but could be guided by isolated adhesive tracks. Growth cone morphology became progressively simpler on progressively narrower single tracks. On narrow period multiple parallel tracks (which did not guide neurite extension) growth cones spanned a number of adhesive/non-adhesive tracks, and their morphology suggests that lamellipodial advance may be independent of the substratum by using filopodia as a scaffold. In addition to acting as guidance cues, laminin micropatterns also appeared to influence the production of primary neurites and their subsequent branching. On planar substrata, dorsal root ganglion neurons were multipolar, with highly branched neurite outgrowth whereas, on 25 microns tracks, neurite branching was reduced or absent, and neuron morphology was typically bipolar. These observations indicate the precision with which growth cone advance may be controlled by substrata and suggest a role for patterned adhesiveness in neuronal morphological differentiation, but also highlight some of the limitations of growth cone sensitivity to substratum cues.

Animals↗
PubMed1993

Chest expansion in healthy adolescents and patients with the seronegative enthesopathy and arthropathy syndrome or juvenile ankylosing spondylitis.

OBJECTIVE: To determine chest expansion measurements in healthy children and those with juvenile spondyloarthropathies. METHODS: Chest expansion, as defined by the difference between maximal inspiration and maximal expiration was measured in 157 healthy adolescents (112 boys and 45 girls) aged 11 to 15 years, 20 patients with the seronegative enthesopathy and arthropathy (SEA) syndrome and 15 with juvenile ankylosing spondylitis (AS). RESULTS: The median and mean chest expansion (+/- 2 SD) were 5.0 cm and 5.6 cm (+/- 3.52) for the whole group of healthy adolescents, 6.0 cm and 5.9 cm (+/- 3.64) for boys and 5.0 cm and 4.8 cm (+/- 2.69) for girls. The frequency distribution of the values was leptokurtic and skewed to the right and did not follow the normal pattern; nearly 90% of the measurements fell within the interval from 3 to 9 cm. Of all variables analyzed (age, height, weight, sex and health/disease status), only height correlated with chest expansion (r = 0.20, p = 0.01). Even so, the effect of all these variables explained only 13% of the total variance of the measurements. Interobserver and intraobserver intraclass correlation coefficients were moderate (0.58 and 0.67, respectively). Mean values and cumulative frequency distribution in asymptomatic and symptomatic SEA syndrome and patients with juvenile AS were similar to those from healthy adolescents. CONCLUSION: Measuring chest expansion does not seem to be a useful method for the rare cases of early involvement of the chest joints in SEA syndrome and juvenile AS.

Adolescent↗
PubMed1993

Use of a DNA probe for the rapid detection of group B streptococci in obstetric patients.

OBJECTIVE: To determine the accuracy of a DNA probe as a rapid diagnostic test for detecting colonization of the female genital tract by group B streptococci during pregnancy. METHODS: Two rayon-tipped applicators were used to collect secretions from the posterior vaginal wall of 440 pregnant women. One of the applicators was inoculated into selective Todd-Hewitt broth and used as the reference standard for identification of group B streptococci. The other applicator was used for analysis with the DNA probe, preceded by either 2.5 hours of incubation for the initial 75 patients, or 3.5 hours' incubation for the remaining women. Following hybridization with an acridinium-labeled probe, chemiluminescence was measured with a luminometer. RESULTS: The prevalence of positive cultures was 20%. For the initial 75 patients whose cultures were amplified by incubation for 2.5 hours, the DNA probe had a sensitivity of 44%, specificity 94%, positive predictive value 79%, and negative predictive value 77%. For the cultures that were incubated for 3.5 hours, respective values were 71, 90, 61, and 94%. All vaginal specimens that had an average initial cell count of 1.5 x 10(3) cells/mL were accurately detected by the probe after 3.5 hours' growth amplification. False-positive results occurred primarily when the specimens were grossly contaminated with blood (26 of 39). The mean time required to perform the assay, including 3.5 hours of growth amplification, was 4.3 hours. CONCLUSIONS: The DNA probe demonstrated good overall sensitivity and gave no false-negative results when group B streptococci were present in concentrations of 1 x 10(4) cells/mL or greater. Sensitivity improved significantly with 3.5 hours' growth amplification as compared with 2.5 hours (P < .05), reflecting better identification of lightly colonized patients.

Carrier State↗
PubMed1992

Alterations in nuclear envelope invaginations in axotomized fetal and early postnatal hamster facial motoneurons.

In this study, changes in the amount of nuclear envelope invaginations (NEI) were morphometrically assessed after axotomy during late fetal and early postnatal developmental stages in hamster facial motoneurons. These changes were expressed as boundary density or BA (length of nuclear envelope per unit area of nucleus). Axotomy-induced changes in nuclear area and perimeter were also quantitatively determined. At 17 h after axotomy in the fetal operative series, no changes in any of the parameters were seen. At 1 day postoperative (dpo) in newborn, 2 and 4 postnatal day animals, the boundary densities of the total and invaginated portion of the nuclear envelope increased significantly. No corresponding qualitative changes were observed. At 2 dpo in 4 and 7 postnatal day animals, there were significant increases in the boundary densities of both invaginated and total nuclear envelope and a decrease in nuclear area. These changes were not seen at 2 dpo in the 9-day operative series. At 4 dpo in 7 and 9 postnatal day animals, scalloping of the normally smooth nuclear profile, as well as a flattening and elongation in nuclear shape, occurred. These qualitative changes in the 7 and 9 day operated groups were also accompanied by significant changes in all the measured parameters. The boundary density of the invaginated, non-invaginated and total nuclear envelope increased; whereas, nuclear area and perimeter decreased. These results argue against the generally held hypothesis that an increase in nuclear envelope invaginations is indicative of an allied increase in cellular metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Structure of HIV-1 reverse transcriptase/DNA complex at 7 A resolution showing active site locations.

AIDS, caused by human immunodeficiency virus (HIV), is one of the world's most serious health problems, with current protocols being inadequate for either prevention or successful long-term treatment. In retroviruses such as HIV, the enzyme reverse transcriptase copies the single-stranded RNA genome into double-stranded DNA that is then integrated into the chromosomes of infected cells. Reverse transcriptase is the target of the most widely used treatments for AIDS, 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI), but resistant strains of HIV-1 arise in patients after a relatively short time. There are several nonnucleoside inhibitors of HIV-1 reverse transcriptase, but resistance to such agents also develops rapidly. We report here the structure at 7 A resolution of a ternary complex of the HIV-1 reverse transcriptase heterodimer, a monoclonal antibody Fab fragment, and a duplex DNA template-primer. The double-stranded DNA binds in a groove on the surface of the enzyme. The electron density near one end of the DNA matches well with the known structure of the HIV-1 reverse transcriptase RNase H domain. At the opposite end of the DNA, a mercurated derivative of UTP has been localized by difference Fourier methods, allowing tentative identification of the polymerase nucleoside triphosphate binding site. We also determined the structure of the reverse transcriptase/Fab complex in the absence of template-primer to compare the bound and free forms of the enzyme. The presence of DNA correlates with movement of protein electron density in the vicinity of the putative template-primer binding groove. These results have important implications for developing improved inhibitors of reverse transcriptase for the treatment of AIDS.

Base Sequence↗
PubMed1992

Dendritic processing: using microstructures to solve a hitherto intractable neurobiological problem.

In vivo, intracellular recordings of mammalian brain stem motoneurones, followed by peroxidase staining and tridimensional reconstruction, suggest that the shape of the dendritic tree plays an important role in the processing of neural information. To test this hypothesis attempts were made to guide, in culture, the growth of neuritic branches of neurones dissociated from the hypoglossal nucleus of rat brain stem. This was performed using topographical and adhesive microstructures which were designed to control the shape of the neuritic tree. Guidance of the neuritic processes can be observed with small grooves engraved on quartz and plastic substrates, and simple shapes with few processes and bifurcations on each neurite could be obtained using adhesive microstructures. These procedures, which allow the shape of a neurone to be controlled, are very promising in the study, by means of classical electrophysiological methods as well as optical recordings, of the involvement of dendritic architecture in the processing of neural information.

Animals↗
PubMed1992

Micropatterned substratum adhesiveness: a model for morphogenetic cues controlling cell behavior.

It is generally considered that tracks of cell adhesiveness are important in controlling cell migration during the development and regeneration of many tissues. In order to investigate this experimentally, a number of techniques have in the past been employed to make patterns of differential adhesiveness for in vitro studies. However, practical limitations on patterning resolution and the introduction of residual topography to the experimental substrata have restricted their usefulness. Here we describe a simplified photolithographic technique for patterning cell adhesiveness which allows a high degree of flexibility and precision. We have quantified, using adhesion and spreading characteristics of BHK cells, the differential adhesiveness that can be created on patterned surfaces, how this alters with the duration of exposure to serum proteins, and how this, in turn, relates to the persistence of cell patterning despite increases in cell density. We believe that this technique will prove extremely useful for the detailed in vitro examination of the mechanisms controlling cell behavior as it offers a degree of precision and ease of fabrication that has previously been unavailable.

Adhesiveness↗
PubMed1992

Thyroid screening tests in psychiatric inpatients.

This study reports on a retrospective evaluation of the current practice of screening for thyroid dysfunction in an adult psychiatric inpatient program. Sixty-four percent of 342 admissions were tested during their hospital stay. Although 13.7% of tests yielded abnormal values on one or more of the thyroid indices, only 0.9% resulted in a diagnosis of hypothyroidism. None of the other abnormal test results led to any specific action being taken. The present pattern of use of thyroid function screening as observed in this study does not appear optimal. Issues in the selection of thyroid screening tests, and the value of the results obtained are discussed.

Adult↗
PubMed1992

Dietary calcium as a statistical determinant of spinal trabecular bone density in amenorrhoeic and oestrogen-replete athletes.

A study investigating the relationship between spinal trabecular bone density (measured by QCT), dietary calcium (measured by questionnaire) and menstrual status in 67 elite female athletes was undertaken. Twenty-five athletes were amenorrhoeic, 27 eumenorrhoeic and 15 were taking an oral contraceptive. The mean bone density was significantly lower (P less than 0.0001) in the amenorrhoeics (168 mg/cm3; 95% confidence interval 154-182) than in the eumenorrhoeics (211 mg/cm3; 197-224) and oral contraceptive takers (215 mg/cm3; 197-233). There was also a significant positive linear correlation between trabecular bone density. However, factors with which calcium intake may be linked, such as energy intake and expenditure, were not measured and therefore it is possible that this relationship is indirect. Further studies on the relationship between dietary calcium and bone mineral density in young women are needed.

Adolescent↗
PubMed1992

Assessment of a rapid latex agglutination test for group B streptococcal colonization of the genital tract.

OBJECTIVE: The purpose of this study was to determine the reliability of a rapid enzyme extraction-latex agglutination test in detecting intrapartum colonization of the maternal genital tract by group B streptococci. METHODS: Swabs of vaginal secretions were obtained from 314 patients in labor with either ruptured or intact membranes. Four tests were performed on each specimen: 1) qualitative culture on blood agar, 2) semiquantitative culture on blood agar, 3) culture in selective Todd-Hewitt broth, and 4) latex agglutination preceded by enzyme extraction. RESULTS: The prevalence of positive cultures was 29%. When compared with culture in Todd-Hewitt broth, the latex agglutination test had a sensitivity of 30%, specificity 93%, positive predictive value 64%, and negative predictive value 76%. In patients with heavy colonization the test had a sensitivity of 76%, compared with 17% in patients with light growth (P less than .001). The lower limit of sensitivity of the test was 4 x 10(5) cfu/mL. The performance of the test was not affected by rupture of the membranes. CONCLUSION: Although the latex agglutination test is reasonably sensitive in detecting heavy colonization, low overall performance combined with technical difficulties in assessment of particle agglutination make the test unsuitable for general screening.

Evaluation Studies as Topic↗
PubMed1992

Cell guidance by micropatterned adhesiveness in vitro.

Tracks of adhesiveness are believed to be involved in guiding morphogenetic cell migrations. Here, electronics microfabrication technology was used to manufacture patterns of alternating tracks of adhesive and non-adhesive substratum (untreated fused quartz and adjacent parallel tracks of hydrophobic treatment) of varying period (4, 6, 12, 24 and 50 microns). These experimental substrata were used to model, in vitro, possible differentially adhesive guidance cues. The effect of such patterned substrata was assessed using fibroblastic BHK cells and epithelial MDCK cells. Cells were oriented and elongated by these surfaces. Their responsiveness was dependent on cell type, cell-cell interactions, and the geometry of the patterns. Alignment of BHK cells increased with increasing pattern period. Single MDCK cells aligned to all pattern periods, their elongation being period-dependent, whereas colonies were mainly unaffected. These in vitro data have important implications, which are discussed with regard to in vivo guidance cues. The ability of cells to bridge over non-adhesive regions will influence the effectiveness of linear cues, and will be important for guideposting. The geometry of patterns of differential adhesion is here shown to be an important factor in determining the precision with which local guidance of cells may be controlled.

Animals↗
PubMed1992

A randomised controlled trial of long stay nursing home and geriatric ward care for the elderly. A summary of main findings.

This paper reports outcome data on mental and physical ability levels, mortality and accidents rates, from a randomised controlled trial evaluating health authority funded nursing home and long stay geriatric ward care in one inner London health district. There were no differences between settings in relation to mortality rates, although respondents randomised to the nursing homes deteriorated more rapidly in overall and functional ability levels; they also experienced a higher accident rate than respondents in the wards. This has to be balanced against the previously published observational data from the evaluation which clearly indicated that quality of life in the homes was superior to that in the wards. There was more occupational therapy input into the wards in comparison with the homes, and activities were promoted most in the patient's Club in the hospital setting. Although quality of life was superior in the homes in relation to flexibility and preservation of resident's dignity.

Accidents↗
PubMed1992

The importance of combining xylene clearance and immunohistochemistry in the accurate staging of colorectal carcinoma.

The prognosis of colorectal carcinoma relies heavily on pathological staging which includes the metastatic state of lymph nodes. Colorectal resectates from 47 patients (41 with colorectal carcinoma and six with non-malignant disease) were entered into a study to assess the best method for detecting metastases in lymph nodes. The maximum number of lymph nodes was harvested at an initial careful examination of the specimen. Subsequently, the pericolic and perirectal fat was dissected out, dehydrated in alcohol, cleared in xylene and further lymph nodes were recovered. Both sets of lymph nodes were examined by the standard histological method and subsequently stained immunohistochemically for cytokeratins (CK). The mean number of lymph nodes recovered at the initial dissection from all 47 cases was 6.7, this was raised to 58.2 after xylene clearance, ie an average of 51.5 lymph nodes were not recovered by traditional methods. At the initial dissection no epithelial cells were detected in any of the lymph nodes from the nonmalignant cases or 25 of the malignant cases. In the other 16 cases, epithelial cells were detected by H&E in 38 lymph nodes. Thus the initial staging was 3 Dukes A, 22 Dukes B and 16 Dukes C. After immunohistochemistry, eight additional cases (originally staged Dukes B) showed epithelial cells in the lymph nodes, these were chiefly occult invasion, raising the involved lymph nodes number to 70. After xylene clearance and applying the CK staining, an additional 135 lymph nodes were found to be involved, thus the overall number of involved lymph nodes was increased to 205. The combined technique changed the Dukes staging in 12 out of 41 cases of colorectal carcinoma, resulting finally in 3 Dukes A, 10 Dukes B and 28 Dukes C, ie 55% of Dukes B become Dukes C.

Antibodies, Monoclonal↗
PubMed1992

Aztreonam.

Aztreonam is a synthetic monobactam antibiotic that has excellent activity against aerobic gram-negative bacilli. It can be used as a single agent for the treatment of upper urinary tract infections caused by organisms resistant to the cephalosporins and ampicillin. It also can be administered in combination with a drug such as clindamycin for treatment of pelvic inflammatory disease or postoperative pelvic infections.

Aztreonam↗
PubMed1992

Assessment of rapid identification tests for genital carriage of group B streptococci.

OBJECTIVE: The purpose of this study was to assess the relative value of reported methods for rapid identification of group B streptococcal colonization of the female genital tract. DATA SOURCES: Trials of group B streptococcal identification techniques published in peer-reviewed journals were located using a computerized literature search and cited references from relevant articles or text chapters. METHODS OF STUDY SELECTION: Reports were included in the analysis if the methodology fulfilled the following criteria: 1) A reference culture method was used for comparison; 2) performance characteristics were presented or could be calculated; 3) the method could be performed in a standard laboratory on a 24-hour-a-day basis; and 4) results could be routinely available within 12 hours. DATA EXTRACTION AND SYNTHESIS: Performance characteristics such as sensitivity, specificity, and predictive values for the various methods were evaluated and compared. Factors such as colonization rates and methods for identifying carriers were included in the overall assessment of test performance. CONCLUSIONS: The overall sensitivity of current methods for the rapid detection of group B streptococcal colonization is low. However, some rapid antigen detection tests are highly sensitive in identifying heavily colonized patients, and therefore may be useful for selecting high-risk patients for intrapartum antibiotic prophylaxis.

Cervix Uteri↗
PubMed1992

Ipsilesional disruptions to reciprocal finger tapping.

Impairments in repetitive finger tapping have not been found in the ipsilesional hand, possibly because the performance measure (tapping rate) which has been used is not sufficiently sensitive. In this study, tapping performance of patients with lateralized brain damage was examined using more detailed measures reflecting intertap variability and the relative timing of each tap cycle. In concert with previous findings, neither the left- nor the right-hemisphere-damaged patients exhibited an impairment in tapping rate. An impairment in tapping variability was observed, however, but only for the left hemisphere group. It is argued that intertap variability may be particularly sensitive to left hemisphere damage as this measure reflects the demands for rather precise and consistent phasing or sequencing of muscle activation. Since left hemisphere damage often leads to deficits in making transitions between movements in a sequence, the consistent sequencing of agonist-antagonist muscle activations in tapping may be compromised. Future research directions to examine this hypothesis are discussed.

Journal Article↗
PubMed1991

Crystals of a ternary complex of human immunodeficiency virus type 1 reverse transcriptase with a monoclonal antibody Fab fragment and double-stranded DNA diffract x-rays to 3.5-A resolution.

Two crystal forms of complexes have been grown that contain human immunodeficiency virus type 1 reverse transcriptase and a monoclonal antibody Fab fragment. One of the crystal forms (form II, space group P3112, a = 168.7 A, c = 220.3 A) diffracts x-rays to 3.5-A resolution and appears suitable for moderate-resolution structure determination. The form II crystals have the unusual property that their maximum resolution of diffraction and resistance to radiation damage are enhanced by either crystallization in the presence of or soaking with double-stranded DNA primer-template mimics. These crystals may permit structural studies of catalytically relevant complexes and eventually enable us to experimentally observe successive steps in the reverse transcription process.

Antibodies, Monoclonal↗