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Biomedical subjects

D J Clark

Publications and source records attributed to D J Clark.

At least 91 records · Page 5Linked to original sources

Alpha-helix in the carboxy-terminal domains of histones H1 and H5.

Although the carboxy-terminal domains of histones H1 and H5 exist as random-coil in aqueous solution, secondary structure prediction suggests that this region has a high potential for alpha-helix formation. We have measured CD spectra in various conditions known to stabilize alpha-helices, to determine whether this potential can be realized in an appropriate environment. Trifluoroethanol increases the helix contents of H1, H5 and their carboxy-terminal fragments, presumably through promotion of axial hydrogen bonding. Sodium perchlorate is also effective and better than sodium chloride, suggesting stabilization by binding of bulky perchlorate ions rather than simple charge screening. Extrapolating from these measurements in solution, and taking into account the occurrence of proline residues throughout the carboxy-terminal domain, we propose that binding to DNA stabilizes helical segments in the carboxy-terminal domains of histones H1 and H5, and that it is this structured form of the domain that is functionally important in chromatin.

Animals↗

Ability of deutan color defectives to perform simulated air traffic control tasks.

Air traffic controllers perform a variety of tasks which require them to identify, discriminate, and name colors. Qualification standards for this occupation require applicants and incumbents to have normal color vision. The validity of this standard has been questioned and is currently under review. In this study, 22 deutans and 78 normals were tested on a set of tasks which simulated critical tasks performed daily by air traffic controllers. The four tasks included discriminating red from black pencil marks on flight progress strips, color-naming of 1 degree and 0.1 degree discs, and identification of colored line segments embedded in a multicolored background. Deutans classified as mild were found to perform all tasks as well as normals. Moderate deutans performed only the large disc color-naming task as well as normals, whereas severe deutans performed none of the tasks as well as normals. Different methods for scoring the color vision tests were explored to determine their value as predictors of task performance. The D-15 relative error score was found to be the single best predictor of performance on the tasks (r-square = 0.602). It is concluded that mild deutan color defectives have adequate color vision for safe performance of several critical air traffic control tasks. Moderate and severe deutans do not. In addition, the results of several methods for scoring color vision tests can be used to predict group, but not individual, performance with high reliability.

Aviation↗

Salt-dependent co-operative interaction of histone H1 with linear DNA.

The nature of the complexes formed between histone H1 and linear double-stranded DNA is dependent on ionic strength and on the H1 : DNA ratio. At an input ratio of less than about 60% (w/w) H1 : DNA, there is a sharp transition from non-co-operative to co-operative binding at a critical salt concentration that depends on the DNA size and is in the range 20 to 50 mM-NaCl. Above this critical ionic strength the H1 binds to only some of the DNA molecules leaving the rest free, as shown by sedimentation analysis. The ionic strength range over which this change in behaviour occurs is also that over which chromatin folding is induced. Above the salt concentration required for co-operative binding of H1 to DNA, but not below it, H1 molecules are in close proximity as shown by the formation of H1 polymers upon chemical cross-linking. The change in binding mode is not driven by the folding of the globular domain of H1, since this is already folded at low salt in the presence of DNA, as indicated by its resistance to tryptic digestion. The H1-DNA complexes at low salt, where H1 is bound distributively to all DNA molecules, contain thickened regions about 6 nm across interspersed with free DNA, as shown by electron microscopy. The complexes formed at higher salt through co-operative interactions are rods of relatively uniform width (11 to 15 nm) whose length is about 1.6 times shorter than that of the input DNA, or are circular if the DNA is long enough. They contain approximately 70% (w/w) H1 : DNA and several DNA molecules. These thick complexes can also be formed at low salt (15 mM-NaCl) when the H1 : DNA input ratio is sufficiently high (approximately 70%).

Allosteric Regulation↗

The ability of protan color defectives to perform color-dependent air traffic control tasks.

Air traffic controllers perform a variety of tasks which require them to identify, discriminate and name colors. Qualification standards for this occupation require applicants to have normal color vision. Although the validity of this standard has been questioned, Adams and Tague recently presented evidence in this Journal (1985;62:744-50) that protanopes cannot perform color-dependent air traffic control tasks reliably. In our study, the results of 7 severe and 2 moderate protans are compared to those of 78 normals on a set of tasks which simulated critical tasks performed daily by air traffic controllers. The four tasks included discriminating red from black pencil marks on flight progress strips, color-naming of 1(0) and 0.1(0) discs, and identification of colored line segments embedded in a multi-colored background. The severe protans we tested performed none of the tasks as well as normals. While the performance of the moderate protans was better, statistical conclusions could not be drawn. Our set of tasks bears many similarities to the set used by Adams and Tague and it appears we were trying to answer the same questions. The results of the two studies are similar and the conclusions are the same: severe protans cannot perform color-dependent air traffic control tasks reliably.

Accidents, Aviation↗

Compound sodium lactate (Hartmann's) solution. Caution: risk of clotting.

We have observed blood clotting in blood administration sets where Hartmann's solution (Travenol) has preceded blood transfusion. This is due to calcium ions (Ca++) contained in the Hartmann's solution and is more likely to occur at 37 degrees C. We suggest that this potential hazard be more widely realised and that the practice cease.

Blood Coagulation↗

The natural history of group B streptococcal colonization in the pregnant woman and her offspring. I. Colonization studies.

A longitudinal study of colonization by group B streptococcus (GBS) was conducted in 93 pregnant women and 92 of their infants. Positive cultures were obtained from vaginal swab specimens on at least one occasion during pregnancy from 20.4% of the women. Three types of carriage were observed: chronic, transient, and intermittent. At the time of delivery, 12.9% of the mothers were colonized by GBS. GBS colonization occurred in 41.7% of the infants of the mothers colonized intrapartum. Only 1.2% of infants intrapartum culture-negative mothers were colonized. Infants colonized at birth were culture negative by 4 months of age. This study suggests that interruption of vertical transmission of GBS from mother to infant not only would influence the incidence of early-onset GBS disease but also might reduce the incidence of late-onset GBS disease.

Adolescent↗

Failure of penicillin to eradicate group B streptococcal colonization in the pregnant woman. A couple study.

Prophylactic treatment of couples with oral penicillin has been recommended as a means of eradicating GBS from the parturient female. In 1977 and 1978 this hypothesis was tested in an investigation of couples from a middle and upper socioeconomic group in Houston, Texas. A group of 40 women, known to be colonized with GBS during the third trimester of pregnancy, and their husbands were treated simultaneously with oral penicillin. Patients were recultured 3 weeks following completion of therapy and at the time of delivery. At the time of delivery 67% of the women remained colonized with GBS. This percentage does not differ substantially from that obtained in a series of untreated colonized women. This study demonstrates that oral penicillin treatment of couples is not an effective means of reducing maternal colonization at the time of delivery.

Delivery, Obstetric↗

Ampicillin prevents intrapartum transmission of group B streptococcus.

Early-onset group B streptococcus (GBS) disease in the infant is acquired by vertical transmission from the mother colonized with GBS. Thirty-four women colonized with GBS were treated with intravenous ampicillin sodium during labor. None of their infants were colonized with GBS at birth or within 48 hours. Twenty-four women colonized with GBS received no antibiotic therapy; 14 (58%) of their infants were colonized with GBS at birth or by 48 hours. This difference was highly significant. Mechanisms by which this may have occurred were temporary suppression of GBS vaginal and rectal colonization, high concentration of ampicillin in the amniotic fluid, and transplacental transport of the antibiotic to the infant. In areas where GBS disease is prevalent, we recommend screening pregnant women (34 to 36 weeks' gestation) and treating those colonized with GBS (with no history of penicillin hypersensitivity) with intravenous ampicillin during labor.

Ampicillin↗

A ten-year assessment of methicillin-associated side effects.

The exact incidence and importance of side effects associated with methicillin therapy in children is unknown. During the ten-year period from 1964 to 1974 approximately 3,000 Houston children who received methicillin were observed for side effects. The great majority of these patients received the drug for less than ten days; however, side effects were more common in patients receiving long-term therapy. In order to assess these side effects, experiences with 124 children who received methicillin for ten days or longer were reviewed in depth. The average dose of methicillin was 200 mg/kg/day and the average duration was 22 days. In this highly selected group there were no adverse side effects in 54.8% and only eosinophilia in an additional 13%. Leukopenia occurred in 16%, microscopic hematuria in 8%, gross hematuria in 4%, skin rash in 6%, and "drug fever" in 6%. In many instances several of these side effects occurred within a single patient so that the total number of patients with definite side effects was 39 of 124 (31.5%). The true incidence figure of overall side effects is much lower than 31.5%. Corrected incidence rates based on a conservative figure of 3,000 methicillin-treated children are less than 1.5% for all side effects. In some patients the mechanism producing the adverse reactions seemed to be chemical irritation or toxicity and in others hypersensitivity. In nine of the 39 patients follow-up studies were not optimal. In the other 30 patients all side effects were reversible.

Adolescent↗

150 MeV proton medical cyclotron design study.

A brief design study has been done for a 150 MeV proton sector cyclotron. The object was to minimize cost but maintain good reliability and easy maintenance. The use of the proton beam would be for therapy, radiography and isotope production.

Nuclear Medicine↗

Incidence of kanamycin resistance among Escherichia coli isolates from neonates.

The antimicrobial susceptibilities of 368 E. coli strains isolated from well neonates, well pediatric outpatients, and ill neonates were determined, and the incidence of antibiotic-resistant strains was correlated with epidemiologic data. Ninety-five per cent of these isolates were susceptible to kanamycin and 98 per cent to gentamicin. Most of the difference in susceptibility of these E. coli strains to kanamycin and gentamicin appeared to be on the basis of weight for weight activity. Kanamycin-susceptible strains were isolated from 96 per cent of well neonates and well outpatients, and 94 per cent of ill neonates, age three days or less. An increase in the incidence of resistance to kanamycin, streptomycin, and ampicillin among strains isolated from neonates was related to prolonged hospitalization and/or prior antibiotic therapy. This study demonstrates the need for analyzing antimicrobial susceptibility data from newborn nurseries in an epidemiologic context.

Child↗

Selective broth medium for isolation of group B streptococci.

A selective medium containing Todd-Hewitt broth, sheep blood, nalidixic acid, and gentamicin sulfate was found to enhance significantly the isolation of group B streptococci from vaginal cultures. Preparation of the medium, which is stable for up to 4 weeks at 4 C, is simple and inexpensive. Use of such a medium should facilitate identification of vaginal colonization with group B streptococci.

Animals↗

Cell growth and division in Escherichia coli: a common genetic control involved in cell division and minicell formation.

Escherichia coli Div 124(ts) is a conditional-lethal cell division mutant formed from a cross between a mutant that produces polar anucleated minicells and a temperature-sensitive cell division mutant affected in a stage of cross-wall synthesis. Under permissive growth temperature (30 C), Div 124(ts) grows and produces normal progeny cells and anucleated minicells from its polar ends. When transferred to nonpermissive growth temperature (42 C), growth and macromolecular synthesis continue, but cell division and minicell formation are inhibited. Growth at 42 C results in formation of filamentous cells showing some constrictions along the length of the filaments. Return of the filaments from 42 to 30 C results in cell division and minicell formation in association with the constrictions and other areas along the length of the filaments. This gives rise to a "necklace-type" array of cells and minicells. Recovery of cell division is observed after a lag and is followed by a burst in cell division and finally by a return to the normal growth characteristic of 30 C cultures. Recovery of cell division takes place in the presence of chloramphenicol or nalidixic acid when these are added at the time of shift from 42 to 30 C, and indicates that a division potential for filament fragmentation is accumulated while the cells are at 42 C. This division potential is used for the production of both minicells and cells of normal length. The conditional-lethal temperature sensitive mutation controls a step(s) in cross-wall synthesis common to cell division and minicell formation.

Cell Division↗

Cell division of Escherichia coli BUG-6: effect of varying the length of growth at the nonpermissive temperature.

When Escherichia coli BUG-6 is grown at 42 C and then returned to 30 C, the division kinetics during the recovery at 30 C are dependent on the length of time the cells were grown at 42 C. If chloramphenicol is added when the cells are shifted from 42 to 30 C, no division occurs if the period at 42 C is less than 4 min or more than 110 min. Maximum division occurs when the period at 42 C is 50 min. A discussion of these results with reference to a previously proposed model is presented.

Cell Division↗