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Biomedical subjects

R Kelly

Publications and source records attributed to R Kelly.

At least 109 records · Page 6Linked to original sources

Nonclonal lymphocytic proliferation in cutaneous lymphoid hyperplasia: a flow-cytometric and morphological analysis.

Cutaneous lymphoid hyperplasia, follicular B cell pseudolymphoma or lymphadenosis benigna cutis and lymphocytic infiltration of Jessner-Kanof are a group of benign lymphoid hyperplastic disorders which usually involve the skin of the face or head and neck. These lesions may be difficult to differentiate from malignant lymphocytic lymphomas both morphologically and clinically. To evaluate whether quantitative flow-cytometric analysis and DNA ploidy determination of the lymphoid cells in the lesions would provide additional and more precise diagnostic parameters, we have correlatively analyzed a case by morphological, flow-cytometric and immunohistochemical methods. The two latter methods both revealed that the lesions harbored nonclonal heterogeneous subpopulations of lymphoid cells, but 62% of the cells analyzed were of B cell lineage progenies. No pre-B cells, immature B or T determinants were detected. Ploidy analysis of the isolated lymphocytes disclosed predominantly diploid (2 N) cells with about 1% 4 N and a few (less than 5%) hyperdiploid (2.2 N) cells. Cell cycle analysis showed that 97.2% of the cells were in G0-G1 phase. Phenotyping and DNA ploidy study of the lymphocytes of the lesion may provide quantitative diagnostic parameters to distinguish this benign lesion from true lymphocytic lymphoma involvement of skin. The eventual biological behavior of the minor hyperdiploid subpopulation of lymphoid cells found in this lesion is currently uncertain, however.

Antibodies, Monoclonal↗

Mosquito size and multiple transmission of avian malaria in the laboratory.

Probing mosquitoes salivate before ingesting blood, and malaria sporozoites are transmitted during this phase of feeding. Large and small Aedes aegypti infected with Plasmodium gallinaceum were allowed to probe briefly on a series of 3 naive chicks. Large mosquitoes were more infective overall, but there was no difference in the ability of either size class to infect the first host. Large mosquitoes were more likely than small mosquitoes to infect more than one host during serial feeding.

Aedes↗

Physician agreement with US Preventive Services Task Force recommendations.

BACKGROUND: No large-scale work has yet assessed the reactions of physicians to the report of the US Preventive Services Task Force (USPSTF), despite its potential for fostering a consensus among practitioners. This study undertook a survey of family physicians to assess their agreement with the recommendations of the Task Force. METHODS: A survey containing the verbatim summary recommendations of the USPSTF was mailed to all 1784 active members of the Ohio Academy of Family Physicians. RESULTS: No evidence of selection bias was found among the 898 responding physicians. The average physician agreed with 88% of the recommendations. For a number of recommendations, however, particularly those in which the Task Force differed with the American Cancer Society, there was a high level of disagreement. Physician disagreement with the recommendations was associated with older age, not having completed a residency, male sex, less prior exposure to the USPSTF guidelines, and greater perception of the impracticality of applying them. CONCLUSIONS: The high level of agreement with most USPSTF recommendations implies that they represent an emerging consensus about which preventive services should be delivered. Attempts at USPSTF guideline dissemination should focus on recommendations with high agreement. Additional research is needed to assess the reasons for disagreement.

Age Factors↗

Spontaneous mutation at the hypervariable mouse minisatellite locus Ms6-hm: flanking DNA sequence and analysis of germline and early somatic mutation events.

Hypervariability at minisatellite loci is maintained by spontaneous mutation to new-length alleles. At the most variable loci, mutation rate is directly measurable by pedigree analysis. The mouse minisatellite locus Ms6-hm has a germline mutation rate of 2.5% per gamete and is therefore one of the most unstable loci yet identified in the mouse genome. Mutation events at this locus also occur during early mouse development, resulting in mice mosaic for cells carrying a common non-parental allele in different somatic tissues and the germline. The DNA sequence flanking Ms6-hm is rich in dispersed repetitive elements; the minisatellite array has expanded from within a member of the Mouse Transcript family which is flanked by two additional Mouse Transcript elements, and a B2 element lies further 3' to the minisatellite. To define the characteristics of mutation events at Ms6-hm we have analysed 19 germline and 13 somatic length-change events. Germline mutation events at Ms6-hm are not accompanied by the exchange of flanking markers in three informative mutant alleles analysed.

Alleles↗

Liquorice.

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11-beta-Hydroxysteroid Dehydrogenases↗

Self-differentiation of human fetal lung organ culture: the role of prostaglandins PGE2 and PGF2 alpha.

Addition of PGE2, but not PGF2 alpha, to fetal lung organ cultures accelerates the process of self-differentiation with increased dilatation of terminal airsacs and differentiation of the epithelial lining. Indomethacin reduces the endogenous production by organ cultures of PGE2, PGF2 alpha, 13,14-dihydro-15-keto-PGE2, and 13,14-dihydro-15-keto-PGF2 alpha and retards the process of self-differentiation. Prolonged exposure of cultures to indomethacin results in cell necrosis. Indomethacin inhibition of self-differentiation can be reversed and accelerated by the addition of PGE2. Addition of PGF2 alpha in the presence of indomethacin prevents indomethacin-associated cell necrosis but does not accelerate dilatation or differentiation beyond that of cultures in sera-free media without additions. We propose that the endogenous production of PGE2 is a key process in the mechanism of self-differentiation of human fetal lung in organ culture.

Cell Differentiation↗

Block of current through single calcium channels by Fe, Co, and Ni. Location of the transition metal binding site in the pore.

The blocking actions of Fe2+, Co2+, and Ni2+ on unitary currents carried by Ba2+ through single dihydropyridine-sensitive Ca2+ channels were recorded from cell-attached patches on myotubes from the mouse C2 cell line. Adding millimolar concentrations of blocker to patch electrodes containing 110 mM BaCl2 produced discrete excursions to the closed channel level. The kinetics of blocking and unblocking were well described with a simple model of open channel block. Hyperpolarization speeded the exit of all of the blockers from the channel, as expected if the blocking site resides within the pore. The block by Ni2+ differs from that produced by Fe2+ and Co2+ because Ni2+ enters the channel approximately 20 times more slowly and exits approximately 50 times more slowly. Ni2+ also differs from the other transition metals because at millimolar concentrations it reduces the amplitude of the unitary current in a concentration-dependent manner. The results are consistent with the idea that the rate-limiting step for ion entry into the channel is water loss at its inner coordination sphere; unblocking, on the other hand, cannot be explained in terms of simple coulombic interactions arising from differences in ion size.

Animals↗

The adequacy of physician reimbursement for pediatric care under Medicaid.

This article examines 1989 Medicaid physician reimbursement for pediatric care in 47 states and the District of Columbia. To assess the adequacy of payment, several state reimbursement policies were analyzed, including physician payment methods, frequency of payment updates, and fee data for five common evaluation and management codes and two Early and Periodic Screening, Diagnosis, and Treatment visit categories. Physician payment rates were evaluated to determine overall state and regional patterns of Medicaid reimbursement. They were also compared with regional private market fee data and average national Medicare fees to assess their adequacy. The majority of state Medicaid programs used fixed fee schedules as their physician reimbursement method. Nearly one fourth of states that update their fees overall by physician specialty have not adjusted their rates since 1985 or before. Medicaid reimbursement rates for five commonly used evaluation and management Physicians' Current Procedural Terminology (4th ed) office visit codes and Early and Periodic Screening, Diagnosis, and Treatment screening and follow-up examinations varied substantially across states and among regions. States in the West paid the highest rates for most office visits, while Northeastern states generally paid the least. A comparison of Medicaid payment rates with private market fee data revealed that Medicaid payments for established patients averaged less than two thirds of market rates for pediatricians, family physicians, and general practitioners. New patient care is reimbursed somewhat better. Regional variations are substantial. In addition, a comparison of Medicaid payment rates with 1988 Medicare fee data showed that average Medicaid reimbursement rates were less than four fifths of average allowed Medicare charges. Policy implications include the need to increase Medicaid rates so that they are much closer to private insurance and Medicare rates, particularly in the Northeast and in selected states, in order to increase participation by pediatric providers in Medicaid. In addition, efforts to re-evaluate reimbursement relative to level of service, as used in Medicare's resource-based relative value scales, deserve further research. Finally, comparable access to comprehensive pediatric care especially in underserved urban areas will require not only improvements in physician reimbursement but also more deliberate efforts to affect the maldistribution of mainstream medical care. Approaches to measure the impact of enhanced reimbursement on access to care by Medicaid-eligible children are discussed.

Delivery of Health Care↗

Cloning and characterization of the 2,3-oxidosqualene cyclase-coding gene of Candida albicans.

2,3-Oxidosqualene (OS) cyclase (OSC) catalyzes the conversion of OS to lanosterol, an essential step in the biosynthesis of sterols. The Candida albicans gene (ERG7) encoding OSC was cloned by complementation of a Saccharomyces cerevisiae OSC mutant (erg7). Two different Erg+ clones were isolated that contain a common overlapping region. The minimum region required for complementation was determined to be approx. 3.2 kb and a single 2.7-kb ERG7 transcript was detected. The cloned Candida ERG7 DNA complemented an additional nonconditional erg7 allele and a temperature-sensitive erg7 mutation. OSC activity was restored in the mutants as determined by [14C]acetate incorporation in vivo as well as incorporation in vitro in cell-free extracts using either [14C]isopentenyl pyrophosphate or [3H]OS as substrate. The level of OSC produced from expression of a single copy of the Candida ERG7 sequence was sufficient to allow growth of the S. cerevisiae erg7 mutants in the absence of exogenous ergosterol. These data support the contention that the Candida ERG7 sequence is the structural gene for OSC.

Alleles↗

The efficacy of social-influence prevention programs versus "standard care": are new initiatives needed?

This study evaluates the effects of a school-based smoking prevention program after 1 year, using school (22 middle/elementary schools, 15 high schools) as both the unit of randomization and the unit of analysis. The multigrade level (grades 6 through 9) intervention was designed to address comprehensively the social influence factors that encourage smoking. Teacher survey data indicated that treatment schools had a median of 10 classroom sessions devoted to tobacco/drug use education, 5 of which were the sessions designed for this evaluation, and control schools had also dedicated a median of 10 classroom sessions to tobacco/drug education. Thus, the study evaluated the incremental effects of the social influence intervention compared to "standard-care" curricula. Among those who reported smoking one or more cigarettes in the month prior to the intervention, there was a significant treatment effect on rate of smoking at one year, but no grade level, gender, or interaction effects. The 1-year covariate-adjusted smoking rate among pretest smokers in the treatment schools was 76.6 cigarettes per month, compared to 111.6 cigarettes per month in control schools, a 31.4% difference. These effects were not accounted for by differential subject attrition. The analyses for nonsmokers, however, showed no significant effects, and the program did not affect self-reported alcohol or marijuana use. Taken together with the results of other prevention studies, these results point to the need for the development and evaluation of new initiatives to prevent substance use.

Adolescent↗

Comparison of antiprogestin stimulation of uterine prostaglandin synthesis in vitro.

Progesterone has an inhibitory effect on prostaglandin synthesis in urine tissue and this effect is reversible with progesterone receptor antagonists. Although antiprogesterone steroids such as RU486 (Mifepristone) are effective at inducing abortion in women they have an improved efficacy when used with exogenous synthetic prostaglandin. In the guinea-pig such antagonists sensitize the uterus but do not result in increased myometrial activity and therefore may not induce endogenous PG synthesis. In this study the effects of antiprogestins on a preparation of rat uterus perifused with progesterone were studied. ZK98 734 caused a rapid and sustained increase in 6-oxoPGF synthesis which rose within the first 90 minutes. This rapid response suggested that some mechanism other than the induction of fresh protein synthesis was involved. A similar increase was not seen with pregnant guinea-pig myometrium/decidua perifused in a similar manner, suggesting that some other mechanism was responsible for the relatively low PG production in pregnancy. However increases in 6-oxoPGF in response to antiprogestins were recorded when pregnant guinea-pig decidua/myometrium was incubated for 4 hours. In these experiments 1 microM ZK98 734 and 1 microM ZK98 299 (Onapristone) gave a 2.7 fold increase in PG production whereas RU486 gave a 1.6 fold increase. Both 1 microM ZK98 734 and 1 microM ZK98 299 also gave a significant increase in PGE production but no increase in PGF was observed. These findings suggest that some antiprogestins might have a better effect on the stimulation of endogenous PG synthesis or on the rate of catabolism of prostanoids.

Animals↗

ECG evidence of limited myocardial infarction following coronary occlusion treated by early intravenous rt-PA infusion.

Serial 12-lead surface electrocardiograms (ECGs) were analysed in 110 patients with first evolving myocardial infarction entered in a double-blind placebo-controlled trial of intravenous rt-PA within 2.5 h (mean 1.9 +/- 0.5 (SD)) of pain onset. ECG analysis was performed by two 'blinded' analysts. QRS scoring (by the modified Selvester method) was used as an index of myocardial necrosis. Patient results were analysed according to infarct location. There was no difference between the two treatment groups in ST-segment elevation or QRS score at entry or up to 24 h after symptom onset. However from 24 h, QRS score was lower in patients with anterior infarction given rt-PA than in those given placebo: 5.4 +/- 2.8 vs 7.7 +/- 4.1 (P = 0.02) at 48 h; 4.7 +/- 3.2 vs 8.0 +/- 4.0 (P = 0.01) at 4-10 days; and 4.6 +/- 3.9 vs 7.5 +/- 3.9 (P = 0.01) at 21 days. For patients with inferior infarction, rt-PA treatment also resulted in a lower QRS score although this was not significantly different from the score of the placebo group (P = 0.07). Comparison of QRS scores with ejection fraction measured from the contrast ventriculogram taken at 21 days showed a moderate correlation (r = 0.46) in patients with anterior infarction but a poor correlation in patients with inferior infarction. These ECG results indicate that in evolving anterior myocardial infarction, there is limitation of infarct size from early rt-PA infusion.

Double-Blind Method↗

Echocardiographic and electrocardiographic study of the normal kangaroo heart.

Healthy kangaroos are prone to sudden death. To investigate possible causes of this phenomenon, echocardiographic and electrocardiographic studies were conducted in seven healthy sedated (intramuscular ketamine 20 mg/kg, xylazine 2 mg/kg) kangaroos aged 1.5-5 years weighing 5.5-48 kg. As in human hypertrophic cardiomyopathy, kangaroos showed relative left ventricular hypertrophy measured as a ratio of (internal left ventricular end-diastolic diameter)/(septal + posterior wall thickness): 1.7 (SD 0.2) in kangaroos and 1.3 (SD 0.4) in hypertrophic cardiomyopathy cf 2.6 (SD 0.6) in normal man (p less than 0.001 respectively). Peak left ventricular diastolic filling velocity was smaller in kangaroos (2.6 (SD 0.3)/sec) and hypertrophic cardiomyopathy (3.3 (SD 0.7)/sec) than in normal man (4.1 (SD 1.0)/sec) (p less than 0.01, p less than 0.05). The end of T wave occurred earlier than the closing of aortic valve. Corrected QT interval (0.20 (SD 0.02) sec) was shorter than the normal value for man (0.34-0.40 sec). In conclusion, kangaroos have cardiac hypertrophy of unknown aetiology, with impaired diastolic function, as in non-obstructive hypertrophic cardiomyopathy patients. Corrected QT interval was short. These echocardiographic and electrocardiographic findings may explain the mechanism of sudden death in kangaroos, a species which may be used as an experimental model of non-obstructive hypertrophic cardiomyopathy in man.

Animals↗

Characterization of a highly unstable mouse minisatellite locus: evidence for somatic mutation during early development.

A highly unstable mouse minisatellite locus, Ms6-hm, has been identified in mouse DNA fingerprints produced by cross-hybridization with human minisatellite probe 33.6. A 7-kb allele of Ms6-hm was cloned from a C57BL/6J mouse and collapsed to a 400-bp plasmid insert on propagation in Escherichia coli due to loss of the majority of minisatellite repeat units. Sequence analysis revealed that Ms6-hm has evolved by amplification within a member of the MT (mouse transcript) family of interspersed repetitive elements. Linkage analysis localized Ms6-hm near the brown coat color gene (b) on chromosome 4. Multiallelism and heterozygosity at this locus within inbred strains result from a high germline mutation rate to new-length alleles (2.5% per gamete). Mice mosaic for cells carrying a nonparental allele in somatic tissue, and in some cases also in the germline, provide evidence for additional, somatic, mutation events at Ms6-hm. In two mosaic mice the fraction of cells containing the nonparental allele has been shown to be indistinguishable in different adult tissues. These somatic mutation events at Ms6-hm must therefore occur very early in development, preceding the allocation of somatic lineages, and the same pool of primitive ectoderm cells must contribute equally to all somatic tissues. Under low-stringency hybridization conditions the collapsed subclone of Ms6-hm cross-hybridizes to other unstable loci in the mouse genome to generate a novel and highly individual specific mouse DNA fingerprint.

Alleles↗