Biomedical subjects
Publications and source records attributed to R Johnson.
The ICD has proved to be a valuable therapeutic adjunct for patients at risk for sudden cardiac death. Careful attention to details associated with patient and family teaching assures a smooth adaptation to what may seem an overwhelming circumstance for patients and family members.
OBJECTIVE: To assess whether a renal graft outcome is dependent on the modality of dialysis prior to transplantation and to assess risk of peritonitis and catheter-related problems posttransplantation. DESIGN: Retrospect analysis of the outcome of a first cadaveric renal transplantation from hemodialysis (HD) and CAPD patients over a ten-year period. PATIENTS: Out of a total of 905 renal transplants over a ten-year period, 699 were first grafts; 500 of these (241 on CAPD, 259 on hemodialysis) were analyzed while the remaining (incomplete data, predialysis, pediatric) were assessed for graft and patient survival only. MAIN OUTCOME: Graft and patient survival cases were identical in the two groups (five-year graft survival: CAPD 67%, hemodialysis 66%; five-year patient survival: CAPD 88%, hemodialysis 87%). CAPD posttransplant was necessary in 37 patients, while 10 developed peritonitis mostly related to CAPD use and responded to appropriate therapy. Routine catheter removal posttransplant was undertaken between 8 and 12 weeks. CONCLUSION: Excellent graft and patient survival is achieved independent of the modality of dialysis prior to transplantation. Peritoneal dialysis can be used postgrafting, but there is a risk of peritonitis, which can be successfully managed with antibiotics and catheter removal. Great care is needed in executing the dialysis and catheter care after transplantation.
Helicases are essential to both DNA replication and transcription because they separate double-stranded DNA, preparing the single strands for replication or transcription. Because the anti-cancer anthracycline antibiotics stabilize double-stranded DNA primarily by their intercalative binding, we expected the intercalated antibiotics to interfere with helicase action. We examined anthracycline antibiotic effects on SV40 large T antigen helicase activity, using a duplex DNA helicase substrate of 32P-labeled 17-mer annealed to complementary M13mp19(+) circular single-stranded DNA. The T antigen helicase activity was potently inhibited by the anthracycline antibiotics. The T antigen helicase IC50 values for the anthracycline antibiotics were as follows: nogalamycin, 2 x 10(-7) M; daunorubicin, 4 x 10(-7) M; doxorubicin, 4 x 10(-7) M; idarubicin, 1.8 x 10(-6) M; 4'-epidoxorubicin, 2 x 10(-6) M; aclacinomycin, 4 x 10(-6) M; and menogaril, 6 x 10(-6) M. Partially purified helicases from HeLa cells and murine mammary carcinoma FM3A cells also were potently inhibited by doxorubicin, with IC50 values of 4 x 10(-7) M and 9 x 10(-7) M, respectively. Because the abundance, specificities, and types of helicases vary in the cell, this site of action for anthracycline antibiotics may help explain anthracycline potency, drug specificity for DNA or RNA inhibition, and some types of cellular resistance to these drugs.
Orofacial pain can have an inflammatory, neurologic or musculoskeletal cause. Inflammatory diseases include dental abscess, sinusitis, temporal arteritis, sialolithiasis and infections of the parotid gland. Common neurologic diseases that cause facial pain are trigeminal neuralgia, glossopharyngeal neuralgia, paratrigeminal neuralgia and cluster headaches. Musculoskeletal causes include temporomandibular joint syndrome and myofascial pain dysfunction syndrome. A clear understanding of pertinent anatomy and an organized approach to diagnosis will facilitate the evaluation of patients with orofacial pain.
OBJECTIVE: To review published abstracts, journal articles, and presentations for evidence of the effects of human immunodeficiency virus (HIV) antibody counseling and testing on risk behaviors. Studies reviewed focused on homosexual men, intravenous drug users in treatment programs, pregnant women, and other heterosexuals. DATA SOURCES: Peer-reviewed journals (January 1986 through July 1990) and published abstracts and oral presentations from the second (1986) through the sixth (1990) International Conferences on AIDS. STUDY SELECTION: We identified 66 studies that included data on the behavioral effects of HIV antibody counseling and testing. By consensus of the authors, 16 of these were excluded because of small sample size or inadequate study design. DATA EXTRACTION: Studies were assessed by the authors according to methodological strength (sample selection, inclusion of appropriate comparison groups, and inclusion of statistical tests of significance). DATA SYNTHESIS: All longitudinal studies of homosexual men reported reductions in risky behavior among both tested and untested men, and a few reported greater decreases among seropositive men than among seronegative men and those untested or unaware of their serostatus. For intravenous drug users in treatment, we found reductions in intravenous drug use and sexual risk behaviors regardless of counseling and testing experience. We found little evidence for the impact of counseling and testing on pregnancy and/or pregnancy termination rates for either seropositive or seronegative high-risk women. We noted substantial risk reduction among heterosexual couples with one infected partner. Findings among other heterosexuals at increased risk were scanty and mixed. CONCLUSIONS: Further studies should specifically address the behavioral consequences of counseling and testing in various settings.
Lifetimes of stimulus-induced conformations of the phototaxis receptor sensory rhodopsin II (SR-II) from Halobacterium halobium are modulated with seven receptor analogues. By monitoring the receptor dynamics in vitro and physiological responses of the cell in vivo, we observe receptor signaling efficiency increases with decreasing cycling frequency (turnover number) of the receptor. The results demonstrate that modulating lifetimes of protein conformations at the SR-II photoactivation site with chromophore analogues alters the lifetime of the active conformation at the signaling site. We further explore the relationship between photocycle intermediates and the signaling efficiency by analyzing the time-averaged concentrations of the two long-lived spectral intermediates of the SR-II photocycle: S-II350 and S-II530. The results are consistent with the signaling site being activated during formation of S-II350, but not reset by the transition of S-II350 into S-II530; rather deactivation appears to require subsequent decay of S-II530. The results indicate the structural changes at the photoactivation site in the S-II350----S-II530 transition do not reset the signaling site. The procedure used here, applicable in principle to any photoactivated or ligand-activated receptor, provides an initial approach to identify structural alterations key to the receptor activation process.
A real-time automated method was developed for simultaneous measurements of phototactic orientation (phototaxis) and step-up photophobic response of flagellated microorganisms. Addition of all-trans retinal restored both photoresponses in a carotenoid-deficient mutant strain of Chlamydomonas reinhardtii in a dose-dependent manner. The phototactic orientation was biphasic with respect to both the light intensity and the concentration of retinal. All-trans retinal was more effective than 11-cis retinal to regenerate both photobehavioral responses. Analogs having locked 11-cis configurations and a phenyl ring in the side chain also induced photoresponses, although at concentrations more than two orders of magnitude higher than all-trans retinal. According to the present assay method, the responses were hardly detectable in cells incubated with retinal analogs in which the 13-ene was locked in either its trans or cis configuration. The results strongly suggest that the isomerization of the 13-14 double bond is important for photobehavioral signal transduction and that a single retinal-dependent photoreceptor controls both phototactic and photophobic responses.
We have determined the exon structure of the mouse tyrosinase-related protein-1 (TRP-1) gene. The gene is only 15kb in length, but contains seven introns, in contrast to the tyrosinase gene which is almost 100kb long with only four introns. Only two introns are located in homologous positions in both genes. Intron I of TRP-1 has three alternative 5' splice sites clustered within 21bp, which all splice to the same 3' site. Intron V has a very unusual 5' splice site, which has the dinucleotide GC rather than the conventional GT. We show that as little as 370bp of 5'-flanking DNA is sufficient to direct cell-specific expression of the chloramphenicol acetyl transferase gene. The flanking DNA of TRP-1, unlike tyrosinase, does not contain a TATA box or a CCAAT box. Both mouse genes, however, share an 11bp sequence, also found in human tyrosinase, which we suggest may be a melanocyte-specific promoter element.
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OBJECTIVE: To examine the requirements and opportunities for obtaining a doctor of medicine or master of surgery degree from a university in the United Kingdom other than the graduate's own, particularly in the case of foreign graduates. DESIGN: Review of regulations governing the award of doctor of medicine and master of surgery degrees in British universities. SETTING: All 19 universities in the United Kingdom offering clinical courses. MAIN OUTCOME MEASURE: Availability of degrees to graduates of other universities. RESULTS: Opportunities for obtaining a degree differed widely among the medical schools, one university (Edinburgh) not admitting graduates of other universities in any circumstance. Of the remaining universities, none would consider a graduate who had not worked in the area where the medical school was located. CONCLUSION: The wide differences in opportunity among the medical schools may put some foreign graduates at a disadvantage compared with other graduates. This problem may become more severe as the number of graduates from the European Community who settle in Britain increases.
The contour of the epicardial coronary vessels may change considerably during coronary angioplasty. We report the extreme and unique "accordion-like" wrinkling of the mid right coronary artery as a result of distal guidewire entrapment during coronary angioplasty. Recognition of this artifact and its treatment may prevent further complications of coronary angioplasty.
We have cloned and characterized three genes (CAR1, CAR2, CAR3) encoding potential cell surface, cyclic adenosine 3':5' monophosphate (AMP) receptors from Dictyostelium discoideum. The three proteins are predicted to be substantially similar in amino acid sequence throughout most of their transmembrane (TM) and loop domains but are distinctly different in their carboxyl terminal segments. In addition, all three genes possess an intron which interrupts an equivalent codon of TM3. CAR1 is expressed early in development when the cAMP relay system is being established. As development proceeds multiple size forms of CAR1 RNA are detected which apparently result from differences in their 5'-untranslated regions. Late in development levels of CAR1 RNA decrease. In contrast, CAR2 encodes a single sized RNA which is expressed only during postaggregative development. CAR3 expression is approximately 10% of CAR1 during early development, is maximal during tight aggregate formation but declines thereafter. Only one size class of CAR3 mRNA is detected throughout development. Because RNA for each of the three genes is present in postaggregative cells, it was of interest to determine the cell type distribution of each RNA. Gene-specific probes were hybridized to RNAs isolated from cells of Percoll gradient-enriched prespore and prestalk fractions and relative levels of hybridization compared. CAR1 and CAR3 show approximately the same pattern of accumulation; a 3-4 fold enrichment in prestalk cells. CAR2, however, is highly enriched in prestalk cells, more than 10 fold relative to prespore cells.
Genome exposure studies were carried out on malignant CHO-K1 and C6 rat glioma cells and their respective, phenotypically normal counterparts (reverse-transformed CHO-K1, and both reverse-transformed C6 glioma and normal rat fibroblasts). Cells were subjected to the nick-translation technique previously developed to make visible the exposed (i.e., DNase I-sensitive) nuclear DNA, and examined by both epifluorescence and confocal microscopy. The confocal microscopy, by permitting examination of sections throughout the nucleus, made possible clearer identification of the regions of exposed and sequestered DNA in the cells studied. A peripheral shell of exposed DNA with some discontinuities was displayed in the great majority of the cells with normal phenotype, but in none of the cancer cells. Both types of cells displayed regions of exposed DNA in the nuclear interior, particularly surrounding the nucleoli. In accordance with previous theoretical proposals we postulate: the peripheral nuclear shell of exposed DNA contains differentiation-specific genes that include the specific growth-control genes and that are functional in normal cells but not in cancer; the exposed genes surrounding the nucleoli may represent housekeeping genes active in both normal and cancer cells; and the DNase I-resistant DNA in the interior of the nucleus we postulate to consist for the most part of genes specific to alternative differentiation states and to be sequestered and inactive. Previous differences in evaluation of roles of peripheral and internal DNA sensitivity to DNAse I hydrolysis appear to be reconciled by this formulation. Identification of exposed DNA may be useful in cancer diagnosis.
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Prostatic tissue was obtained from 36 patients at two study locations and assayed for azithromycin by HPLC or bioassay. The mean concentration of azithromycin in human prostatic tissue (2.54 micrograms/ml) 14 h after 500 mg oral dosing (two 250 mg doses 12 h apart) was much greater than plasma concentrations (less than or equal to 0.1 micrograms/ml). Azithromycin was slowly eliminated from prostatic tissue (half-life 60 h) and a mean concentration of 0.62 micrograms/ml remained 137 h after dosing.
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In separate studies of arithmetic and mental rotation, similar posterior negative slow waves have been found. This similarity was surprising given the difference in cognitive processing required by these tasks. Furthermore, delayed responses were employed in these studies, so that it was not possible to determine the extent to which the slow wave activity was too late to be associated with processing that was specific to performance of the tasks. This experiment was intended to clarify the task-specific and non-specific nature of the slow wave activity. Subjects performed either an arithmetic or mental rotation task at two levels of difficulty on a random, trial-to-trial basis and gave an immediate response. There were a number of late posterior negativities, each with a different timing and topography, which were sensitive to type of task and/or task difficulty. Some components were associated with early task processing that was synchronized to the stimulus while others, revealed by response-synchronized averaging, were associated with later stages of task processing. There also was post-task activity that was sensitive to the difficulty level of the prior operations. In both tasks, there was a pre-frontal positive wave that persisted over most of the pre-response epoch, evidently related to a process that was active throughout the task. There also was centro-frontal phasic negativity, with a large peak at 380 msec in mental rotation, and a smaller, longer latency peak in arithmetic, apparently related to the complexity of the stimulus. Thus we conclude that arithmetic and mental rotation each elicit task-specific slow wave activity.
Intraosseous infusion is a temporary procedure for use in pediatric emergencies when intravenous access is difficult. Multiple drugs and fluids can be safely administered through the intraosseous route. Dosage and rate of infusion are essentially the same as with intravenous infusion.