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Biomedical subjects

H D Jones

Publications and source records attributed to H D Jones.

At least 37 records · Page 2Linked to original sources

Crystal structure of cyclin-dependent kinase 2.

Cyclin-dependent kinase 2 (CDK2) is a member of a highly conserved family of protein kinases that regulate the eukaryotic cell cycle. The crystal structures of the human CDK2 apoenzyme and its Mg2+ ATP complex have been determined to 2.4 A resolution. The structure is bi-lobate, like that of the cyclic AMP-dependent protein kinase, but contains a unique helix-loop segment that interferes with ATP and protein substrate binding and probably plays a key part in the regulation of all cyclin-dependent kinases.

Adenosine Triphosphate↗

Video microscopy of organelle inheritance and motility in budding yeast.

By adapting the time-lapse video microscopy techniques that were developed for larger, more complex cells, to living Saccharomyces cerevisiae cells, intracellular organelle movements were observed. Differential interference contrast optics revealed an organelle transport process in cells treated with mating pheromone. Small particles were observed to travel distances of up to 6 microns at rates of 0.11-0.17 (and in one case 0.80) micron/sec. Overall, the frequency of these motile events was quite low compared to what is observed in cell types traditionally studied by video microscopy. The ability to discern clearly the vacuole and nucleus in budding yeast revealed the dynamics of these organelles and the fact that their movements are carefully orchestrated during the cell cycle. Two types of vacuolar dynamics were observed: 1) interconversion between one large organelle and numerous smaller organelles and 2) the formation of projections that extend from the mother cell's vacuole into the bud. When applied to the study of the many available cytoskeletal and cell cycle mutants, the application of video microscopy to the study of organelle movements in living yeast cells will provide a unique opportunity to determine the molecular mechanisms of intracellular motility and to elucidate the temporal controls over these processes.

Biological Transport↗

Actin structure and function: roles in mitochondrial organization and morphogenesis in budding yeast and identification of the phalloidin-binding site.

To further elucidate the functions of actin in budding yeast and to relate actin structure to specific roles and interactions in vivo, we determined the phenotypes caused by 13 charged-to-alanine mutations isolated previously in the single Saccharomyces cerevisiae actin gene. Defects in actin organization, morphogenesis, budding pattern, chitin deposition, septation, nuclear segregation, and mitochondrial organization were observed. In wild-type cells, mitochondria were found to be aligned along actin cables. Many of the amino acid substitutions that had the most severe effects on mitochondrial organization are located under the myosin "footprint" on the actin monomer, suggesting that actin-myosin interactions might underlie mitochondrial organization in yeast. In addition, one mutant (act1-129; R177A, D179A) produced an actin that assembled into cables and patches that could be visualized by anti-actin immunofluorescence in situ and that assembled into microfilaments of normal appearance in vitro as judged by electron microscopy but which could not be labeled by rhodamine-phalloidin in situ or in vitro. Rhodamine-phalloidin could label actin filaments assembled from all of the other mutant actins, including one (act1-119; R116A, E117A, K118A) that is altered at a residue (E117) that can be chemically cross-linked to phalloidin. The implication of residues R177 and/or D179 in phalloidin binding is in close agreement with a recently reported molecular model in which the phalloidin-binding site is proposed to be at the junction of two or three actin monomers in the filament.

Actin Cytoskeleton↗

Assessment of the drug interaction between intravenous nitroglycerin and heparin.

OBJECTIVE: To assess whether a clinically significant interaction occurs between heparin and nitroglycerin (NTG). METHODOLOGY: Activated partial thromboplastin time (APTT) was measured in patients with unstable angina who were stabilized on intravenous NTG and heparin just prior to weaning the NTG infusion, and one and four hours after stopping the NTG. RESULTS: In 22 heparin-treated patients (20 men, 2 women; aged 56.7 +/- 10 years; weight 79.5 +/- 15 kg), the APTT ratio was inversely related to the dose of NTG (slope = -0.003; p < 0.05). However, there were no significant differences between the APTT values measured before and after discontinuation of NTG (p = 0.8511). CONCLUSIONS: Our study demonstrates a clinically insignificant interaction between NTG and heparin at NTG doses commonly used in patients.

Aged↗

Reorganizing to provide pharmaceutical care.

We feel the reorganization has enabled us to position the department and, more importantly, the individual practitioner to achieve a practice model that approaches the pharmaceutical care paradigm. As a result of the reorganization, our department is now structured around patient care and has in place teams of pharmacists, technicians, and managers who have the potential to be proactive and collaborative with other health care professionals to improve the drug therapy outcomes of our patients.

Decision Making, Organizational↗

Effects of 2 mg and 4 mg atropine sulfate on the performance of U.S. Army helicopter pilots.

Atropine autoinjectors are issued to aviators for use in the event of organophosphate poisoning on the battlefield. This investigation assessed the effects of unchallenged 2 mg and 4 mg doses on flight performance, vision, tracking, cognitive performance, and electroencephalograms of 12 Army aviators. Effects were seen most often with the 4 mg dose in terms of aircraft control problems, vision disturbances, impaired tracking, reduced cortical activation, and decreased cognitive skill. These problems indicate helicopter tactical flight is dangerous after an unchallenged 4 mg dose. Other types of flight should also be avoided for at least 12 h after atropine.

Adult↗

In-vitro susceptibility of 400 isolates of Neisseria gonorrhoeae in Vancouver, 1982-84.

Consecutive isolates of Neisseria gonorrhoeae obtained at a sexually transmitted disease clinic in Vancouver between June 1982 and June 1984 were tested for in-vitro susceptibility to eight antimicrobial agents. Of the 400 isolates 6 (1.5%) were penicillinase-producing N. gonorrhoeae, and for 25 (6.2%) the minimum inhibitory concentrations (MICs) of penicillin were 1.0 to 4.0 micrograms/ml. Ceftriaxone sodium was the most active agent. The MICs were higher than those reported in a Canadian study in 1973-74, except for tetracycline hydrochloride. The patterns of susceptibility of the isolates to one antimicrobial agent correlated significantly with those to each other agent, although the relation was weakest for trimethoprim-sulfamethoxazole and spectinomycin. The results reinforce the need to evaluate local in-vitro susceptibility patterns, especially since the proportion of isolates with relative and absolute resistance to penicillin is increasing.

Anti-Bacterial Agents↗

Efficacy of treatment regimens for lower urogenital Chlamydia trachomatis infection in women.

One hundred thirteen women had Chlamydia trachomatis isolated from the cervix, or urethra, or both, were treated, and followed until failure occurred or for at least 40 days after initiation of treatment. On regimens given four times daily for 7 days, failure occurred in three (8%) of 38 on tetracycline, 500 mg, in none of five on erythromycin, 500 mg, and in three (8%) of 37 on erythromycin, 250 mg. On regimens of 500 mg given four times daily for 10 days, failure occurred in none of nine on tetracycline and in one (4%) of 24 on sulfisoxazole. Erythromycin, 500 mg, was stopped because of severe side effects. Another 10 women were given a loading dose of ampicillin plus additional ampicillin for 3 to 21 days and were followed for 4 to 76 days after treatment was stopped. Only two women remained culture positive after therapy. This study demonstrates that antimicrobial regimens that are frequently given to women in North America have significant activity against C. trachomatis.

Anti-Bacterial Agents↗

Tetracycline in nongonococcal urethritis. Comparison of 2 g and 1 g daily for seven days.

In a previous study treatment with minocycline 100 mg orally every day for seven days was as effective for nongonococcal urethritis (NGU) as 200 mg for seven days or 100 or 200 mg for 21 days. In this prospective, randomised study men with NGU received tetracycline either 500 mg or 250 mg four times daily for seven days. of 200 men initially enrolled, Chlamydia trachomatis was isolated from 40% and Ureaplasma urealyticum from 48%. Eight of 10 homosexual men compared with 39 (21%) of 190 bisexual or heterosexual men had negative culture results for both C trachomatis and U urealyticum (x2 = 15.5, P < 0.0005). U urealyticum was isolated more frequently from chlamydia-negative men and from men with 10 or fewer sex partners during their lifetime. Both regimens were equally effective in their in-vivo activity against C trachomatis and U urealyticum. Failure rates were similar with the two regimens. More obvious failure with purulent or profuse mucoid discharge and pyuria occurred more frequently with the 250-mg regimen (20% of 76 men on the 250-mg regimen compared with 7% of 67 men on the 500-mg regimen; x2 = 4.45, P < 0.05). Failure occurred more frequently in men who were initially chlamydia-negative and in men in whom U urealyticum persisted after medication. Thus, the 250-mg regimen appeared to be as effective as the 500-mg regimen in the initial treatment of NGU. However, one-third of men had persistent or recurrent urethritis with these regimens, and there is a need for antimicrobial agents with greater in-vivo activity, especially against chlamydia-negative NGU.

Chlamydia trachomatis↗

Partial efficacy of clindamycin against Chlamydia trachomatis in men with nongonococcal urethritis.

Tetracyclines are the drugs of choice for treatment of Chlamydia trachomatis infection, but alternative antimicrobial agents are needed. Clindamycin has moderate in-vitro activity against C. trachomatis. In this study clindamycin (600 mg orally three times daily for seven days) was given to 76 men with nongonococcal urethritis. Initial microbiologic and clinical responses were significantly better in men from whom C. trachomatis was initially isolated, compared with men from whom Ureaplasma urealyticum was initially isolated, but by 42 +/- 7 days after initiation of treatment, persistence or recurrence of urethritis had occurred in 39% of men with either organism initially isolated. C. trachomatis was ultimately reisolated at follow-up evaluation from seven of 23 men who initially had had positive cultures for C. trachomatis. There was no apparent relationship between the in-vitro susceptibility of C. trachomatis and the ultimate response. These results indicate that clindamycin cannot be relied upon to eradicate C. trachomatis from men with urethritis.

Adult↗