P-A-C-E yourself: tips on time management.
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Humans↗
Biomedical subjects
M Lynch
Publications and source records attributed to M Lynch.
Management of the upper airway.
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Humans↗
Inhibition of IgA1 proteinases from Neisseria gonorrhoeae and Hemophilus influenzae by peptide prolyl boronic acids.
The alpha-aminoboronic acid analog of proline has been synthesized and incorporated into a number of peptides as the COOH-terminal residue. These peptide prolyl boronic acids are potent inhibitors of both the type 1 and type 2 IgA proteinases from Neisseria gonorrhoeae and Hemophilus influenzae, but not of the functionally similar IgA proteinase from Streptococcus sanguis. The best inhibitors synthesized thus far have Ki values in the nanomolar range (4.0 to 60 nM). These results indicate that the N. gonorrhoeae and the H. influenzae enzymes belong to the serine protease family of proteolytic enzymes while that from S. sanguis does not. As a group, the IgA proteinases have been noted for their remarkable specificity; thus, the peptide prolyl boronic acids reported here are the first small synthetic molecules to exhibit a relatively high affinity for the active site of an IgA proteinase and are therefore the first to yield some insight into the active site structure and specificity requirements of these enzymes.
Amino Acid Sequence↗
An analysis of invalidity benefit claim durations for new male claimants in 1977/1978 and 1982/1983.
This study analyses the duration of Invalidity Benefit (IVB) claims commencing in 1977/1978 and 1982/1983 using a hazard rate model. The analysis was carried out against a background of a substantial increase in the numbers claiming IVB. The main data base comprises a 1% random sample of all National Insurance records for the period 1975-1984, provided by the DHSS. Estimates are made of factors that influence claim durations. The results suggest that while age and health conditions are important, claim durations are also influenced by more narrowly defined economic considerations.
Actuarial Analysis↗
Changing water-use patterns in a water-poor area: lessons for a trachoma intervention project.
An epidemiological survey carried out in the Dodoma region of Tanzania found that high rates of trachoma infection in pre-school children were associated with unwashed faces. Prior to a planned trachoma intervention project, a pilot study was done on household decisions about water use and perceptions about face washing and eye disease. The study found that mothers overestimated the amount of water necessary to wash a child's face. In addition, mothers would not change their water-use priorities without the consent of their husbands and the support of the community. Therefore a health education program was designed to address the perception that face washing required a great deal of water. The program also sought to involve and re-educate the whole community rather than focus only on the mothers who were most likely to wash the children's faces.
Child↗
High progesterone receptor concentration in a variant of the ZR-75-1 human breast cancer cell line adapted to growth in oestrogen free conditions.
Culture of ZR-75-1 human breast cancer cells for 5 days in the absence of oestrogens (phenol red-free medium supplemented with dextran coated charcoal stripped 5% fetal calf serum) resulted in a slowing of growth rate and loss of progesterone receptors. Oestradiol at 10(-9) M markedly stimulated growth and progesterone receptor synthesis over a 5-day period. While medroxyprogesterone acetate (10(-10) to 10(-6) M) inhibited growth of ZR-75-1 cells growing in complete medium, in the short-term absence of oestrogens low concentrations were growth stimulatory. Cells deprived of oestrogens for 5 days retained sensitivity to growth inhibition by 4-hydroxy tamoxifen. ZR-75-1 cells were also adapted to growth in the absence of oestrogens over a 5-month period. These cells (ZR-PR-LT) failed to express binding sites characteristic of the type 1 oestrogen receptor but progesterone receptor expression was at a level normally associated with oestrogen induction. Adapted cells were growth inhibited by oestradiol, 4-hydroxy tamoxifen and medroxyprogesterone acetate, but despite elevated progesterone receptor expression the progestin was only marginally more inhibitory than in the parent line. Our data indicate a poor quantitative relationship between response to progestins in vitro and progesterone receptor concentration and support previous findings that acquisition of an oestrogen independent phenotype does not necessarily result in resistance to anti-oestrogens.
Antineoplastic Agents↗
The analysis of population survey data on DNA sequence variation.
A technique is presented for the partitioning of nucleotide diversity into within- and between-population components for the case in which multiple populations have been surveyed for restriction-site variation. This allows the estimation of an analogue of FST at the DNA level. Approximate expressions are given for the variance of these estimates resulting from nucleotide, individual, and population sampling. Application of the technique to existing studies on mitochondrial DNA in several animal species and on several nuclear genes in Drosophila indicates that the standard errors of genetic diversity estimates are usually quite large. Thus, comparative studies of nucleotide diversity need to be substantially larger than the current standards. Normally, only a very small fraction of the sampling variance is caused by sampling of individuals. Even when 20 or so restriction enzymes are employed, nucleotide sampling is a major source of error, and population sampling is often quite important. Generally, the degree of population subdivision at the nucleotide level is comparable with that at the haplotype level, but significant differences do arise as a result of inequalities in the genetic distances between haplotypes.
Animals↗
Hierarchical analysis of population genetic variation in mitochondrial and nuclear genes of Daphnia pulex.
The geographic structure of Daphnia pulex populations from the central United States is analyzed with respect to isozyme and mitochondrial DNA variation. The species complex consists of cyclic and obligate parthenogens. A hierarchical analysis of population structure in the cyclic parthenogens by using a fixation-index approach indicates that this is one of the most extremely subdivided species yet studied. This genetic structure, much of which accrues within 100 km, is certainly due in part to the limited dispersal ability of Daphnia. However, previous work has shown that fluctuating selection can account for the spatial heterogeneity in isozyme frequencies in these populations. This may explain why the population subdivision for the mitochondrial genome increases approximately three times as rapidly with distance as does that for nuclear genes, which is slower than the neutral expectation. The obligate parthenogens are shown to be polyphyletic in origin, evolutionarily young, and, in some cases, geographically widespread.
Animals↗
The similarity index and DNA fingerprinting.
DNA-fingerprint similarity is being used increasingly to make inferences about levels of genetic variation within and between natural populations. It is shown that the similarity index--the average fraction of shared restriction fragments--provides upwardly biased estimates of population homozygosity but nearly unbiased estimates of the average identity-in-state for random pairs of individuals. A method is suggested for partitioning the DNA-fingerprint dissimilarity into within- and between-population components. Some simple expressions are given for the sampling variances of these estimators.
Alleles↗
The repeated sequence CATT(A/T) is required for granulocyte-macrophage colony-stimulating factor promoter activity.
The hematopoietic growth factor GM-CSF (granulocyte-macrophage colony-stimulating factor) is expressed by activated but not resting T lymphocytes. Previously, we localized GM-CSF-inducible promoter activity to a 90-bp region of GM-CSF 5'-flanking sequences extending from bp -53 to +37. To more precisely identify the GM-CSF DNA sequences required for inducible promoter activity in T lymphocytes, we have performed mutagenesis within a region of GM-CSF 5'-flanking sequences (bp -57 to -24) that contains the repeated sequence CATT(A/T). Mutations that do not alter the repeated CATT(A/T) sequence do not eliminate inducible promoter activity, whereas mutation or deletion of either of the CATT(A/T) repeats eliminates all inducible promoter activity in T-cell lines and in primary human T lymphocytes. Thus, both copies of the direct repeat CATT(A/T) are required for mitogen-inducible expression of GM-CSF in T cells.
Animals↗
Torulopsis glabrata vaginitis: clinical aspects and susceptibility to antifungal agents.
Torulopsis glabrata is second only to Candida albicans in frequency of isolation from the vagina in both asymptomatic women and patients with yeast vaginitis. We retrospectively studied 33 patients from whom vaginal isolates of T glabrata were obtained. Torulopsis glabrata caused symptomatic vaginitis in 42% of the patients but was unassociated with symptoms in 30%; in 27% of patients, its importance was uncertain because of concomitant pathology. Antifungal susceptibility testing was performed on 39 T glabrata strains isolated from 39 patients. The minimal inhibitory concentrations (MICs) of the majority of T glabrata isolates fell within the sensitive range of the antimycotic drugs tested; however, no correlation was found between in vitro antifungal MICs and the response to azole drug therapy. Clinical success was achieved in 67% of the patients although mycologic cure occurred in only 33%. A small number of patients developed recurrent and often chronic Torulopsis vaginitis unresponsive to conventional therapy. Limited experience suggests that vaginal boric acid therapy may be of value in these recalcitrant cases.
Adult↗
Teaching the value of water in disease control.
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Child↗
Hygiene factors and increased risk of trachoma in central Tanzania.
Trachoma remains the major infectious cause of blindness in many developing areas, especially where hygiene is poor. The practices and behaviors associated with an increased risk of trachoma were studied in central Tanzania, where a stratified random cluster sample of 8409 people was examined. Data were collected on family and individual characteristics and behaviors and on trachoma status. Overall, 60% of the children aged 1 to 7 years had active inflammatory trachoma, and 10% of those aged 60 years or older had trichiasis. Regression analysis showed that active inflammatory trachoma in children was associated with the characteristics of the more traditional families and several measures of poor personal hygiene. Two important risk factors for severe inflammatory trachoma were poor facial cleanliness in children (odds ratio of 1.7 [1.17, 2.50]) and household fly density (odds ratio of 1.63 [1.17, 2.29]). Both factors are potentially amenable to intervention. These data suggest that an intervention strategy aimed at these hygiene measures would provide an effective method of controlling trachoma in this region, and a similar approach may be useful in other areas.
Adult↗
Tetrapeptide inhibitors of the IgA1 proteinases from type I Neisseria gonorrhoeae.
The six series of unique tetrapeptides and their blocked N-acetyl, C-amide, and N-acetyl-C-amide analogues which comprise the hinge region of human IgA1 (Ser224 to Ser240) have been synthesized and tested as inhibitors of the type 1 IgA1 proteinase elaborated by Neisseria gonorrhoeae (EC 3.4.24.13). Most series had at least one member with an IC50 value less than 1 mM. The most effective inhibitors came from the series Ser-Thr-Pro-Pro (P4-P1) and Pro-Thr-Pro-Ser (P1-P3'). One member from each series had an IC50 value in the low microM range. Magnetic resonance studies (Siemion, I. Z.; et al. Biophys. Chem. 1988, 31, 35) indicate that the various tetrapeptide series appear to have different preferred solution conformations. However, these do not appear to be correlated with affinity for the neisserial proteinase. The most effective inhibitors tend to have a threonine residue adjacent to the N-terminus and the P1 or P1' residues at either the N- or the C-terminus. These relationships are not exclusive however, as other inhibitors, which do not meet these criteria, bind reasonably well. The most effective substrate analogues outlined here are about one-half the size and bind to the neisserial proteinase 2 orders of magnitude more tightly than previously reported inhibitors.
Amino Acid Sequence↗
Characterisation of a tamoxifen-resistant variant of the ZR-75-1 human breast cancer cell line (ZR-75-9a1) and ability of the resistant phenotype.
A 6-month exposure of ZR-75-1 human breast cancer cells to tamoxifen (1 microM rising to 2 microM). resulted in a fall in oestrogen receptor (ER) levels from 225 fmol mg protein-1 to 56 fmol mg protein-1 while progesterone receptor (PGR) concentration fell from 63 fmol mg protein-1 to undetectable levels. Sensitivity to the anti-proliferative effects of tamoxifen was unchanged. A further 6 months' exposure to 4 microM tamoxifen resulted in loss of detectable ER and PGR and development of resistance to tamoxifen. Resistant cells, designated ZR-75-9a1, displayed morphological changes consistent with the acquisition of a less well differentiated phenotype. Flow cytometric studies demonstrated that the cell cycle distribution pattern of the resistant variant growing in the presence of 8 microM tamoxifen was identical to that of the untreated parent line, which showed marked accumulation of cells in G0/G1 when exposed to 8 microM tamoxifen. The resistant phenotype was not stable if cells were transferred to complete drug-free medium, but remained stable for at least 3 months in the presence of medium lacking oestrogenic activity. ZR-75-9a1 cells differ from previously reported tamoxifen-resistant variants of the MCF-7 line which retain ER and may prove a valuable model for the study of the development and stability of tamoxifen resistance in human breast cancer.
Breast Neoplasms↗
Patterns of maxillofacial injuries in restrained and unrestrained motor vehicle crash victims.
Safety belts reduce the frequency and severity of injuries sustained in motor vehicle crashes. Since the head and face are the most frequently injured anatomic regions in motor vehicle crash victims, the use of active restraints should lessen these injuries. This study was undertaken to examine the ability of safety belts to prevent and alter the pattern of maxillofacial injuries. During a 6-month period beginning February 1, 1987, 613 motor vehicle crash victims presented alive to the Trauma Center at the University of Tennessee Medical Center at Knoxville and were entered into this study. There were 254 restrained victims (R), 290 unrestrained (UR), and 69 who were excluded for lack of sufficient data regarding restraint usage. Unrestrained victims tended to be younger (mean age: UR = 27.9, R = 31.7; p less than 0.03), and more often male (UR = 65% vs. R = 51%; p less than 0.03). Irrespective of position within the vehicle, the mean number of facial lacerations per person was less in the restrained group (R = 0.31, UR = 0.76; p less than 0.03). This injury reduction was more pronounced in front seat occupants (R = 0.27, UR = 0.82; p less than 0.03). Furthermore, a smaller proportion of the lacerations in the restrained group were categorized as complex, i.e., involving more than skin and subcutaneous tissue (R = 5.0%, UR = 15.9%; p less than 0.03). The pattern of skeletal injuries was also significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
Accidents, Traffic↗
Injury and cost comparison of restrained and unrestrained motor vehicle crash victims.
The use of active motor vehicle restraints is a topic of current public and legislative debate. To better define the effects of restraint systems on injury severity, the following study was undertaken. Parametric statistical tests were used for data analyses. For a 6-month period beginning February 1, 1987, all motor vehicle crash victims treated in the emergency unit were entered into the study (n = 613). There were 290 unrestrained subjects (UR), 254 restrained subjects (R), and 69 were excluded because restraint usage information was unobtainable. Unrestrained victims were younger (mean age, UR = 28, R = 32; p less than 0.05), and were more often male (UR = 65%, R = 51%; p less than 0.05). Hospitalization was more frequently required for unrestrained crash victims (UR = 59%, R = 26%; p less than 0.05). Length of hospital stay (LOS), including ICU confinement, was also extended (mean LOS, UR = 13, R = 10), but this difference did not reach statistical significance. Injury Severity Scores (ISS) and Abbreviated Injury Scales (AIS) were tabulated and compared. Mean ISS was significantly higher for unrestrained victims (UR = 8.28, R = 4.44; p less than 0.05), and a higher proportion of unrestrained victims had scores greater than 15 (UR = 20%, R = 7%; p less than 0.05). Mean AIS was higher in all regions, although the difference did not consistently reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Accidents, Traffic↗
Grace under pressure. Drills become reality during California's 'quake and Hurricane Hugo.
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California↗