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Biomedical subjects

R Kelly

Publications and source records attributed to R Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

Rapid diagnosis of Aujeszky's disease in pigs by improved in situ hybridization using biotinylated probes on paraffin-embedded tissue sections.

A practical in situ hybridization (ISH) method has been developed for the rapid diagnosis of pseudorabies virus (PRV) infection in pigs. The method utilizes routine formalin fixed and paraffin-embedded tissue sections, non radioactive biotin-labelling, simple hybridization procedure and diaminobenzidine (DAB) silver enhancement detection system. The rapid (ISH) method showed concordance with the direct filter hybridization (DFH) and with the peroxidase-antiperoxidase (PAP) assays. By the simplified ISH, diagnosis can be made within two days.

Animals↗
PubMed1989

Noninvasive determination of age-related changes in the human arterial pulse.

Arterial pressure waves were recorded noninvasively from the carotid, radial, femoral, or all three of these arteries of 1,005 normal subjects, aged 2-91 years, using a new transcutaneous tonometer containing a high fidelity Millar micromanometer. Waves were ensemble-averaged into age-decade groups. Characteristic changes were noted with increasing age. In all sites, pulse amplitude increased with advancing age (carotid, 91.3%; radial 67.5%; femoral, 50.1% from first to eighth decade), diastolic decay steepened, and diastolic waves became less prominent. In the carotid pulse, there was, in youth, a second peak on the downstroke of the waves in late systole. After the third decade, this second peak rose with age to merge with and dominate the initial rise. In the radial pulse, a late systolic wave was also apparent, but this occurred later; with age, this second peak rose but not above the initial rise in early systole, even at the eighth decade. In the femoral artery, there was a single systolic wave at all ages. Aging changes in the arterial pulse are explicable on the basis of both an increase in arterial stiffness with increased pulse-wave velocity and progressively earlier wave reflection. These two factors may be separated and effects of the latter measured from pressure wave-contour analysis using an "augmentation index," determined by a computer algorithm developed from invasive pressure and flow data. Changes in peak pressure in the central (carotid) artery show increasing cardiac afterload with increasing age in a normal population; this can account for the cardiac hypertrophy that occurs with advancing age (even as other organs atrophy) and the predisposition to cardiac failure in the elderly. Identification of mechanisms responsible offers a new approach to reduction of left ventricular afterload.

Aging↗
PubMed1989

Arterial dilation and reduced wave reflection. Benefit of dilevalol in hypertension.

We compared dilevalol (an isomer of labetalol), 200-400 mg daily, against atenolol, 50-100 mg daily, in a double-blind, crossover, placebo-controlled trial with respect to effects on arterial distensibility (measured as pulse wave velocity [PWV]) and wave reflection (assessed from carotid pressure wave contour). Twelve patients of mean age 58 years (range 44-73 years) with essential hypertension (supine diastolic blood pressure 95-114 mm Hg) took active therapy for 12 weeks, separated by a 2-4 week placebo period. Carotid pressure waveforms were recorded noninvasively by applanation tonometry with a Millar micromanometer-tipped probe. PWV was measured between carotid and femoral arteries (aortic PWV), carotid and radial arteries (arm PWV), and femoral and pedal arteries (leg PWV). Early wave reflection was calculated from the ratio of the height of the peak of the carotid wave above its shoulder to the pulse pressure and was expressed as an augmentation index. Both drugs were equally effective in reducing brachial sphygmomanometric pressure and PWV in all three regions (active vs. placebo, p less than 0.001), but there was no significant difference between the two active therapies. However, the augmentation index (averaged during the treatment period) was significantly lower with dilevalol (19%) than with atenolol (28%, p less than 0.01), corresponding to a greater decrease of 5-8 mm Hg in carotid systolic pressure compared with the brachial artery. Although both drugs were equally effective in reducing arterial distensibility, the vasodilating action of dilevalol gave added benefit in reducing wave reflection, presumably through its vasodilatory effect on peripheral conduit arteries.

Adult↗
PubMed1989

Laparotomy in infertility patients with endometriosis. Use of the CO2 laser.

Sixty-eight women underwent laparotomy for endometriosis associated with infertility. They were not candidates for laser laparoscopy by our criteria, or they had failed to conceive after previous therapy. The cumulative pregnancy rate was 70% at 48 months. Patients who failed to conceive after previous laparotomy and those who failed to conceive after previous medical therapy experienced 44% and 28% term pregnancy rates, respectively, after laparotomy using the CO2 laser. Thus, for women who have failed to conceive after major surgical procedures, repeat surgery may offer a greater chance of conception than do multiple cycles of in vitro fertilization/embryo transfer.

Adult↗
PubMed1988

One-step gene disruption by cotransformation to isolate double auxotrophs in Candida albicans.

The Candida albicans LEU2 gene was disrupted by substituting lambda DNA for a small deletion within the LEU2 gene. Cotransformation with a selectable URA3 ARS vector was used to introduce a linear fragment containing the disruption into the genome of a C. albicans ura3 deletion mutant. Cotransformants containing the lambda DNA were identified by colony hybridization and the URA3 plasmid was subsequently cured. Leu2 disrupted heterozygotes were detected by Southern hybridization and one disruptant was subsequently treated with UV irradiation. Only one leu2 ura3 mutant (SGY-484) was isolated out of 11,000 mutagenized cells. SGY-484 was transformed to Leu+ with either the C. albicans or Saccharomyces cerevisiae LEU2 gene. Southern hybridization analysis revealed that the mutant is not homozygous for the disruption; the leu2 mutation reverts and is most likely a point mutation. Unexpectedly, an ade2 ura3 mutant was isolated from the same mutagenesis.

Bacteriophage lambda↗
PubMed1988

Prognostic value of pre-ovulatory serum progesterone, LH and oestradiol-17 beta levels in stimulated cycles for in-vitro fertilization.

The prognostic value of a decrease in oestradiol-17 beta (E2) on the day after HCG injection in stimulated cycles has been related to a premature increase in plasma progesterone (P) on the day before HCG injection. This retrospective study was carried out on 363 patients who were divided into four groups. Patients in group A were given clomiphene citrate plus human menopausal gonadotrophin (HMG) to stimulate follicle growth, and they were subdivided into subgroups A1 and A2 who showed an increase or a decrease in E2 levels after HCG injection. The changes in E2 were greater than 10% of the levels on the previous day. Patients in group B were stimulated by HMG and were similarly subdivided into subgroups B1 and B2 according to their E2 levels. The number of oocytes recovered and the incidence of pregnancy was significantly higher in A2 as compared with A1, and higher but not significantly so in B2 versus B1. Moreover, in subgroups A1 and B1 the day before the decrease of E2 was marked by a significant rise in LH before the HCG injection. We suggest that oocyte recovery is deferred in these cases.

Adult↗
PubMed1988

Limitation of myocardial infarction by early infusion of recombinant tissue-type plasminogen activator.

In a double-blind randomized trial involving five Sydney hospitals and the city ambulance paramedical service, 145 patients with a first evolving myocardial infarction and with onset of pain less than 2.5 (mean 1.9 +/- 0.5 [SD]) hr previously were allocated to intravenous infusion of 100 mg recombinant tissue-type plasminogen activator (rt-PA) or placebo over 3 hr. The groups at entry were similar. At assessment 21 days later, left ventricular ejection fraction measured both by contrast and radionuclide ventriculography was higher in the rt-PA compared with the placebo group (61 +/- 13%, n = 64, vs 54 +/- 14%, n = 62, contrast, 2p = .006; 52 +/- 13%, n = 66, vs 48 +/- 13%, n = 62 isotope, 2p = .08). This indicates limitation of myocardial infarction by rt-PA.

Adult↗
PubMed1988

The molecular genetics of Candida albicans.

Candida albicans, the major fungal pathogen of humans, is a diploid with no known sexual cycle. Recent genetic studies in C. albicans include the physical characterization of the genome, the development of systems for parasexual genetics, the cloning of Candida genes, and the development of methods for integrative and ARS-mediated transformation as well as gene disruption.

Candida albicans↗
PubMed1988

Nortriptyline in the treatment of panic disorder and agoraphobia with panic attacks.

Thirty-four consecutive patients with panic disorder or agoraphobia with panic attacks were treated with nortriptyline at the LAC-USC Medical Center's Anxiety Disorders Clinic. Fourteen (67%) of the 21 completers totally lost their panic attacks, five (24%) showed partial improvement, and two (10%) showed no improvement. The relationship of treatment outcome to pretreatment and posttreatment measures of depression is discussed, in addition to the potential role of nortriptyline in treating panic attacks in clinical practice.

Adult↗
PubMed1988

Organ blood flow haemodynamics and metabolism of the albacore tuna Thunnus alalunga (Bonnaterre).

Metabolic haemodynamic, and organ blood flow measurements were made in tabled, partially anaesthetized albacore Thunnus alalunga. Heart rates were 115 +/- 9 beats/min: blood pressure 98/75 mm Hg (systolic/diastolic): cardiac output 36.1 +/- 5 (ml/min/kg): oxygen consumption 3.4 +/- 0.7 (ml O2/min/kg) and cardiac contractility (dP/dt) 6342 +/- 822 mm Hg/s. Organ blood flows were measured with radiolabelled microspheres. The red muscle, kidney, and spleen received the highest flows and the white-muscle the least. There was a flow gradient in the white-muscle with the inner portion near the red-muscle receiving the highest flows. Arterial and venous blood gas measurements showed a reverse temperature effect on arterial PO2 and a P50 of 15.9 Torr corrected to 37 degrees C. Red-muscle temperature was 7 degrees C higher than ambient water temperature. These measurements record the albacore's markedly high cardiovascular capability.

Animals↗
PubMed1987

Mouse DNA 'fingerprints': analysis of chromosome localization and germ-line stability of hypervariable loci in recombinant inbred strains.

Human minisatellite probes cross-hybridize to mouse DNA and detect multiple variable loci. The resulting DNA "fingerprints" vary substantially between inbred strains but relatively little within an inbred strain. By studying the segregation of variable DNA fragments in BXD recombinant inbred strains of mice, at least 13 hypervariable loci were defined, 8 of which could be regionally assigned to mouse chromosomes. The assigned loci are autosomal, dispersed and not preferentially associated with centromeres or telomeres. One of these minisatellites is complex, with alleles 90 kb or more long and with internal restriction endonuclease cleavage sites which produce a minisatellite "haplotype" of multiple cosegregating fragments. In addition, one locus shows extreme germ-line instability and should provide a useful system for studying more directly the rates and processes of allelic variation of minisatellites.

Animals↗