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Biomedical subjects

M Kelly

Publications and source records attributed to M Kelly.

At least 343 records · Page 19Linked to original sources
PubMed1983

Inhibition of ornithine decarboxylase induces embryonal carcinoma cell differentiation.

Murine embryonal carcinoma cells can be induced to differentiate in vitro by various physical and chemical means. We report here that inhibition of ornithine decarboxylase activity with a specific enzyme-activated inhibitor, alpha-difluoromethylornithine, can induce differentiation in embryonal carcinoma cells. The differentiated phenotype can be distinguished from undifferentiated embryonal carcinoma cells by altered cellular morphology, biochemical and cell surface antigenic properties. These results suggest that alterations in the levels of cellular polyamines may play a role in embryonal carcinoma cell differentiation.

Animals↗
PubMed1983

Specific high-affinity binding and biologic action of retinoic acid in human neuroblastoma cell lines.

Neuroblastoma cells are a good model for neuronal development because of their ability to extend neurites in response to various stimuli, including retinoic acid. In the present experiments, we have examined five human neuroblastoma cell lines (LA-N-1, IMR-32, LA-N-5, SK-N-MC, and CHP-100) for the presence of cellular retinoic acid binding protein (CRABP), a receptor-like protein implicated in the molecular functioning of vitamin A. CRABP is identified and quantitated by sucrose gradient centrifugation, selective inhibition by the mercurial reagent p-chloromercuribenzene sulfonic acid (PCMBS), and saturation analysis. All five lines contain significant levels of cytosolic CRABP (2.5-7.5 pmol/mg of protein), which display typical properties of specific high affinity retinoic acid binding, a sedimentation coefficient of 2 S, and inhibition by PCMBS. Three of the lines (LA-N-1, IMR-32, and LA-N-5) are strongly growth inhibited by 1 microM retinoic acid in monolayer culture, whereas two (LA-N-1 and LA-N-5) undergo marked differentiation to a stellate, fusiform morphology with characteristic neurite outgrowths. The SK-N-MC and CHP-100 lines are relatively resistant to the antiproliferative effects of retinoic acid under these conditions. Nevertheless, all five lines are effectively inhibited by retinoic acid in their ability to form anchorage-independent colonies in soft agar. Thus, although CRABP is not necessarily correlated with growth inhibition in monolayer culture, it is associated with retinoic acid's ability to inhibit neuroblastoma colony formation in soft agar. More experiments will be required to determine if this effect on growth in soft agar reflects the putative ability of retinoic acid to convert tumorigenic neuroblastoma cell lines into the normal differentiated phenotype.

Carrier Proteins↗
PubMed1983

Nucleotide sequence of the 3' end of MCF 247 murine leukemia virus.

We isolated DNA clones of MCF 247, a leukemogenic, recombinant type C virus obtained from the thymus of an AKR mouse. We determined the nucleotide sequence of the viral long terminal repeat (LTR) and the 3' end of env, and we compared the sequences to corresponding sequences of the genome of Akv virus, the putative ecotropic parent of MCF 247. By analogy with Moloney leukemia virus, we identified the amino terminus of Prp15E, the C-terminal proteolytic cleavage product of env and precursor to mature virion p15E. In MCF 247 the presumptive Prp15E is encoded by a 603-nucleotide open reading frame. The majority of this sequence is identical to that of Akv. However, a recombination event near the 3' end of the Prp15E-coding region introduces nonecotropic sequences into MCF 247, and these extend to the 3' end through the U3 portion of the LTR. The U3 regions of Akv and MCF 247 are about 83% homologous. The R and U5 regions of the LTR of MCF 247 and Akv are identical. Large RNase T1-resistant oligonucleotides analyzed previously in numerous ecotropic and MCF viral genomes were located within the Akv and MCF 247 DNA sequences. The resulting precise T1 oligonucleotide maps of the 3' ends of MCF viral genomes reveal that the biologically defined, leukemogenic class I MCFs isolated from thymic neoplasms of inbred mice all share the sequence pattern seen in MCF 247, a representative of this group; they possess recombinant Prp15E genes and derive U3 from their nonecotropic parents.

Amino Acid Sequence↗
PubMed1983

Evaluation of the dopamine response to stress in man.

Because the role of circulating dopamine (DA) in the sympathetic nervous system response to stress remains unclear, alterations in peripheral DA concentrations were determined in healthy volunteers after assuming upright posture (n = 6), hand immersion in ice water (cold pressor, n = 6), and insulin-induced hypoglycemia (n = 11) and in 17 comatose patients with severe brain injury (11 head trauma and 6 intracranial hemorrhage). Changes in DA levels were compared to increases in epinephrine (E) and norepinephrine (NE), all of which were measured by the radioenzymatic technique. The minimum sensitivities were 42, 22, and 38 pg/ml, respectively. In 19 normal men and 22 women, basal DA levels were below assay sensitivity in 31 and were 85 +/- 7 (+/- SE) pg/ml in the remainder. Plasma E was measurable in all but 7 subjects, with a mean concentration of 41 +/- 4 pg/ml. NE levels were 201 +/- 17 pg/ml in 30 of the 31 subjects in whom it was detectable. There was no sex difference for any of the catecholamines. Upon standing, neither DA nor E changed significantly, but NE, increased by 176 +/- 40 pg/ml (P less than 0.0025). There were no significant changes in DA or E concentrations during the cold pressor test, while NE increased by 212 +/- 66 pg/ml (P less than 0.025). Compared to the E (1044 +/- 356 pg/ml; P less than 0.02) and NE (233 +/- 62 pg/ml; P less than 0.005) increments after hypoglycemia, the maximal DA increment, although significant (62 +/- 22 pg/ml; P less than 0.025), was less than those of the other catecholamines. DA levels were measurable in only 7 of 40 samples from 17 brain-injured patients and was 72 +/- 13 pg/ml in the remainder. However, E and NE levels were detectable in 79% of the samples and were significantly greater than normal (125.6 +/- 14 and 594 +/- 59 pg/ml; P less than 0.001, respectively). It is concluded that basal DA levels are generally below the assay limits of detectability. Furthermore, measurement of circulating levels suggests that DA participates in the general sympathetic response only when the adrenal component is maximally activated.

Adolescent↗
PubMed1983

Loss of adrenocortical suppression after acute brain injury: role of increased intracranial pressure and brain stem function.

The function of the pituitary-adrenal axis was studied in 23 acutely brain-injured, comatose patients (14 head trauma and 9 intracranial hemorrhage), who were treated with dexamethasone (16-64 mg/daily). Patients with normal intracranial pressure (ICP) and normal brain stem function (group 1) had decreased plasma cortisol levels (less than or equal to 5 micrograms/dl) within 36 h (mean +/- SEM, 2.4 +/- 0.3 microgram/dl; t 1/2, 18 h). In contrast, patients with elevated ICP (i.e. greater than 20 mm Hg; midline shift, or compressed ventricles) and normal brain stem function (group 2) had persistently elevated cortisol concentrations (15.4 +/- 2.6 micrograms/dl; P less than 0.001). Superimposition of brain stem dysfunction resulted in generally low cortisol levels regardless of the presence (group 4; 3.9 +/- 1.0 microgram/dl; P less than 0.001 compared to group 2) or absence (group 3; 2.1 +/- 0.5 microgram/dl) of elevated ICP. Plasma ACTH levels in 31 samples obtained before or during dexamethasone therapy in 14 patients irrespective of group were not elevated (45.6 +/- 12.5 pg/ml); there was no correlation between plasma ACTH and cortisol levels. Despite elevated cortisol values in group 2, ACTH levels were low (22.4 +/- 10.1 pg/ml). It is concluded that elevated ICP in the presence of normal brain stem function is a potent stimulus for adrenocortical activation which is not associated with elevated ACTH levels, and that the brain stem is involved in this response.

Adrenal Cortex↗
PubMed1983

Persistence of cholera in the United States.

In 1973, 1978, and 1981, cases of cholera were acquired along the Gulf Coast of the United States. The isolates from all of the cases were toxigenic Vibrio cholerae O-group 1, biotype El Tor, serotype Inaba, hemolytic, and of the same phage sensitivity pattern, and all had the same restriction endonuclease pattern by molecular genetic analysis. The strain from one of the two 1981 cases differed from the others in having a small plasmid and a negative Voges-Proskauer reaction. Multiple importations, chronic carriers, and continuous occurrence of undetected cases are unlikely explanations for these findings, which suggest that toxigenic V. cholerae 01 can multiply and persist for years in some environments, making eradication of cholera a formidable task.

Adult↗
PubMed1982

Limb load monitor: evaluation of a sensory feedback device for controlled weight bearing.

In order to evaluate usefulness of the Limb Load Monitor (LLM), an auditory feedback device, in a prescribed weight-bearing program, a clinical study was conducted. Results were divided into objective and subjective findings. Objective findings substantiated that both the study group and control group reached established goals, but the study group reached goals twice as fast. Subjective findings indicated that the device served to remind and assume the patient that weight bearing was being performed as prescribed.

Adult↗
PubMed1981

Impact of hepatitis on renal transplantation.

In order to delineate the incidence, etiology, and impact of liver disease in renal transplant patients, we reviewed 405 consecutive transplants performed between 1970 and 1980. Hepatic dysfunction of at least 2 weeks' duration was diagnosed in 42 patients (10.4%). Of 28 patients acquiring hepatitis in the first post-transplant year, 26 (92.8%) developed chronic hepatitis; of 14 acquiring hepatitis after the first year, 9 (64.2%) developed chronic hepatitis. Of the 42 patients, 19 (45.2%) died, as compared with 16% of the nonhepatitis patients (P less than 0.001). Only one of these patients died of liver failure, with 15 of the 19 (78.9%) dying of extrahepatic infection. In addition, 12 of the 23 survivors (52.1%) suffered life-threatening infections from which they recovered, as compared with 20% of the nonhepatitis patients (P less than 0.01). Conversely, graft survival was significantly increased among the hepatitis patients (73% 1-year cadaveric allograft survival as compared with 50% for the nonhepatitis patients (P less than 0.01)). The etiology of the liver disease was identified in the minority of patients: 5 (11.9%) with hepatitis B, with none occurring since 1973; 10 (23.8%) with evidence of cytomegalovirus infection; and 1 (2.3%) with azathioprine toxicity. We conclude that the major cause of liver disease in renal transplant patients is non-A, non-B hepatitis, and furthermore, that this disease has a marked immunosuppressing effect resulting in increased allograft survival and a marked increase of life-threatening extrahepatic infection.

Diagnosis, Differential↗
PubMed1981

Ca++ inhibition of isoproterenol responses in mammalian skeletal muscle.

In noncontracting mouse hemidiaphragms incubated in modified Krebs-Ringer--bicarbonate buffer with 10 mM Ca++, isoproterenol-stimulated phosphorylase a formation, conversion of phosphorylase kinase to the activated form, elevation of cyclic AMP-dependent protein kinase activity ratios and increase in cyclic AMP concentrations were reduced 35 to 50% over the responses in buffer with 2.5 mM Ca++. In buffer with 10 mM Ca++, the initial rate of isoproterenol-stimulated cyclic AMP accumulation was 59% of that in buffer with 2.5 mM Ca++. The inhibitory action of Ca++ on cyclic AMP accumulation was antagonized by verapamil, but not by inhibitors of cyclic nucleotide phosphodiesterase activity. In buffer with 2.5 mM Ca++, isoproterenol-stimulated cyclic AMP accumulation was inhibited by A23187 and caffeine, agents that can increase intracellular Ca++ concentrations. In addition to Ca++, high concentrations of Co++, Ni++, Mn++ and, to a lesser extent, Sr++ inhibited the isoproterenol response. The results of these studies indicate that high buffer Ca++ concentrations inhibit the response of the glycogenolytic pathway to isoproterenol by an action on cyclic AMP formation. We propose that the site of the inhibitory action of Ca++ is the divalent metal activator site associated with hormone-stimulated adenylate cyclase activity.

Animals↗
PubMed1980

Isotope angiocardiography of the left ventricle.

Radionuclide imaging of the left ventricle is a recent innovative procedure requiring a gamma-camera interfaced to a computer. It has the advantages of being non-invasive and of allowing studies at rest and exercise. Left ventricular function may be assessed by viewing the images as an endless loop cine-display, or by quantitating the over-all and segmental functions. Validation studies comparing the technique with standard contrast angiograms have confirmed its reliability. Clinical studies have been undertaken in normal volunteers, and in patients. The technique will have increasing application in assessing the aetiology of chest pain, in selection of patients for cardiac surgery, and in determining the effects of interventions, such as drug therapy or coronary artery bypass surgery, on ventricular performance.

Adult↗