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Biomedical subjects

K Gordon

Publications and source records attributed to K Gordon.

At least 181 records · Page 10Linked to original sources

Mathematical and statistical aids to evaluate data from renal patients.

The monitoring of renal patients and the making of many decisions during their management involves consideration of sequences of numerical data. Renal function results after renal transplantation were used as an example of how graphical presentations, simple mathematical transforms, statistical evaluation and adjustments to the data, to take into account other biological and technical sources of error, can all contribute to better understanding. Experience with a statistical technique, the 4-state Kalman filter not often used in the biological sciences, was summarized and its use suggested as a method to quantitate some traditionally subjective decisions about individual patients, for example, the onset of allograft rejection. The method has identified in retrospect and in prospect events after transplantation earlier than did experienced clinicians. Other statistical techniques to set the sensitivity and specificity of monitoring methods, to detect change points and to quantitate rhythmic sequences of clinical data were discussed, with examples, and with increasing access to computers, these can be used more easily by nephrologists, transplant surgeons, and others.

Computers↗

Campylobacter enterocolitis in New Orleans.

Campylobacter is being increasingly recognized as a common pathogen producing acute diarrheal illness. During 1981, all stool cultures at Charity Hospital were routinely screened for Campylobacter. Twenty-nine of 2,233 total cultures were positive. We performed a retrospective study to evaluate the disease's clinical picture and epidemiologic features. Campylobacter-positive cultures comprised 1.3% of all stool specimens and 21.6% of all positive cultures. Age, sex, and race in the Campylobacter group did not differ significantly from a comparison group. The distribution of the rates of Campylobacter-positive cultures did not show temporal trends. The clinical symptoms were nonspecific and the disease was usually self-limited, with diarrhea lasting from seven to ten days in untreated patients. The disease may occasionally be confused with a nonspecific inflammatory bowel disease. Thus, it is important that stool cultures be routinely screened for Campylobacter so that appropriate therapy can be administered.

Adolescent↗

Specific small nuclear RNAs from SV40-transformed cells stimulate transcription initiation in nontransformed isolated nuclei.

Previous studies in our laboratory have implicated small nuclear RNAs (SnRNA) in the regulation of transcription in isolated mammalian cell nuclei. The present investigation was designed to develop a transcription assay system using isolated intact nuclei with optimized RNA polymerase II activity which would be capable of reinitiation in vitro to study the mode of action of the "active" RNA. We used nuclei isolated from either human W138 or Balb 3T3 mouse cells to test the activity of SnRNA purified from SV40-transformed W138 or 3T3 cell lines. These systems were found to support transcription up to 60 min, 40--60% of which was polymerase II dependent. In vitro initiations were detected by [gamma-32p]ATP incorporation as well as by Hg-Sepharose chromatography using (gamma-S)ATP as substrate. Results supported the following conclusions: (a) SnRNA from transformed cells stimulates the transcriptional activity of nontransformed nuclei while homologous SnRNA has little or no activity; (b) the stimulation is NaOH-sensitive and is dependent on RNA polymerase II since it is eliminated by 1 microgram/ml alpha-amanitin; (c) the active subfraction of SnRNA from mouse cells was found to be of identical size (320--350 nucleotides) to that previously identified in human and monkey cells; and (d) analysis of the transcripts obtained from control and stimulated cell nuclei revealed that SnRNA activity is due primarily to an increase in the number of initiated chains.

Animals↗

Fractionation and identification of spinach chloroplast transfer RNAs and mapping of their genes on the restriction map of chloroplast DNA.

Spinach chloroplast 4S RNAs has been separated by two-dimensional polyacrylamide gel electrophoresis into about 35 species. After extraction from the gel, 27 of these RNA species were identified by aminoacylation as tRNAs specific for 16 amino acids. Individual tRNAs were labeled in vitro with 125I and hybridized to DNA fragments obtained by digestion of spinach chloroplast DNA with KpnI, PstI, SalI and XmaI restriction endonucleases. A minimum of 21 genes corresponding to tRNAs for 14 different amino acids have been localized on the restriction endonuclease cleavage site map of the DNA molecule. Of these, 15 genes corresponding to tRNAs for 12 amino acids are located in the larger of the two single-copy regions which separate the two inverted copies of the repeat region. Each copy of this repeat region contains a set of genes for the ribosomal RNAs and a gene for tRNA2Ile in the "spacer" sequence between the 16S and 23S ribosomal RNAs. The genes for tRNA1Ile, tRNA2Leu and tRNA3Leu also map in the repeat region, but outside the ribosomal DNA unit. At present, two more chloroplast tRNAs (for Pro and Lys) have been identified, but not mapped, while 4 unidentified 4S RNAs have been mapped in the large single-copy region of the DNA molecule. Evidence is presented that isoaccepting tRNA species can be transcripts from different loci.

Amino Acyl-tRNA Synthetases↗

Freebased cocaine smoking and reactive airway disease.

The case of a 19-year-old white female who presented with marked respiratory distress and pleuritic chest pain following freebased cocaine smoking is presented. A ventilation-perfusion scan revealed radioactive aerosol trapping in the large airways with multiple ventilation defects of the small airways, a finding compatible with reactive airway disease of the large airways and concomitant mucous plugging of the small airways. Freebased cocaine, impurities of the freebasing process, or admixtures to the freebased cocaine provided prior to smoking, are proposed as possible etiologies in what appears to be a condition of environmentally induced reactive airway disease, a previously unreported effect of cocaine use.

Adult↗

Psychiatric morbidity following motor vehicle accidents: a review of methodological issues.

Motor vehicle accidents (MVAs), even those of a nonserious nature, appear to increase the risk of severe psychiatric morbidity in survivors. The present review examines the evidence indicating the levels of psychiatric morbidity in MVA survivors. Although no consistent profile has emerged, the most commonly reported symptoms are depression, anxiety, irritability, driving phobia, anger, sleep disturbances, and headache, with rates of posttraumatic stress disorder (PTSD) across studies of 0% to 100%. Variability in the type and severity of psychiatric outcomes may be due, in part, to methodological inadequacies in many studies, particularly the use of biased population samples, inclusion of subjects exposed to varied types of accidents, an absence of a clear definition of PTSD, a reliance on clinical judgment rather than the use of objective psychometric measures, the failure to include ratings of injury severity, and the absence of assessments for past exposure to traumatic events or preexisting posttraumatic reactions. The most important concern relates to the use of nonrepresentative samples, usually patients referred for medicolegal assessment in whom issues of compensation are of central importance. Gender and age differences distinguish the compensation group from the general population of MVA survivors, who therefore may also differ in the vulnerability to posttraumatic morbidity. It is argued that more systematic research on unselected subject samples is critical to establish epidemiological data on the true nature and extent of psychiatric morbidity following MVAs.

Accidents, Traffic↗

Polycyclic phenols, estrogens and neuroprotection: a proposed mitochondrial mechanism.

Polycyclic phenols, including the estrogens, have been shown to be potent neuroprotectants in a variety of cellular and animal model systems. Although classical estrogen receptor interactions and consequent responses play a role in certain circumstances, the neuroprotective activity of polycyclic phenols that do not interact with estrogen receptors ERalpha or ERbeta is more likely to be through non-genomic mechanism(s). We propose here that such non-feminizing polycyclic phenols exert their protective effects at least in part by stabilizing mitochondria, preventing apoptotic and/or necrotic forms of cell death that are associated with mitochondrial dysfunction. Consistent with this mitochondrial model and the available data, these compounds protect neurons and other cell types from a wide variety of pathologically relevant stressors.

Adenosine Triphosphate↗

Phenolic A ring requirement for the neuroprotective effects of steroids.

Estrogens are reported to reduce the incidence of Alzheimer's disease and 17beta-estradiol (betaE2), the potent, naturally occurring estrogen, exerts neuroprotective effects in a variety of in vivo and in vitro model systems. The present study elucidates the structural requirements of steroids and related compounds for neuroprotectivity at low nM doses. All estrogens tested with an intact phenolic A ring protected SK-N-SH neuroblastoma cells from the toxic effects of serum-deprivation. All 3-O-methyl ether cogeners tested were inactive indicating the importance of a phenolic A ring. The diphenolic estrogen mimic diethylstilbesterol (DES) was neuroprotective and retention of a single phenolic function was sufficient to retain neuroprotective activity. The di-O-methyl ether of DES was inactive. The following steroids which lack a phenolic A ring were also inactive: testosterone; dihydrotestosterone; progesterone; corticosterone; prednisolone; 6 alpha-methylprednisolone; aldosterone; and cholesterol. Finally, phenol, lipophilic phenols, and tetrahydronapthol were inactive. These results suggest that a phenolic A ring and at least three rings of the steroid nucleus are necessary for the neuroprotective activity of estrogens.

Estradiol↗

Allergic rash due to antiepileptic drugs: clinical features and management.

Optimal management of allergic rash from antiepileptic drugs (AEDs) is unclear. We identified 50 patients with 68 reactions (36 to one AED, 10 to two AEDs, and four to three AEDs). The AEDs implicated were carbamazepine, 30; phenobarbital (PB), 20; phenytoin, 16; ethosuximide, one; and AED combination, one. Sixty-three reactions were cutaneous eruptions, three exfoliative dermatitis, and two Stevens-Johnson syndrome. Forty-six reactions were mild (rash only), 18 moderate (systemic symptoms or other organ system involvement), and four life-threatening (all with PB). In most patients with greater than 1 reaction, the second and third reactions were not more severe than the first. Prior antibiotic allergies or nonmedication allergies were no more common than in a control group without reactions. The AED was ceased abruptly in 59 patients (22 of whom did not receive a new AED), tapered in five, and continued unchanged in four. Despite this, there was no status epilepticus (SE) during the reaction or its treatment, and no patient's seizure control deteriorated. In 40 cases, a new AED was added--16 after the reaction had resolved and 24 before total resolution. Rash recurred with the new AED in 50 and 42% respectively (NS). We conclude that, though allergic rashes to AEDs are usually mild, the rare occurrence of severe reactions indicates that the AED should be ceased. This can be done abruptly with minimal risk of SE. A new AED can be added, if necessary, prior to the resolution of the rash without increasing the risk of further reactions.

Adolescent↗

In vivo effects of a potent GnRH antagonist ORG 30850: physiologic evidence that down-regulation of GnRH receptors does not occur.

OBJECTIVE: Our purpose was to determine the pituitary responsiveness to exogenous GnRH in GnRH antagonist-suppressed ovariectomized monkeys. METHODS: This was a prospective experimental non-human primate study performed at the research laboratories of The Jones Institute for Reproductive Medicine. Seventeen long-term ovariectomized cynomolgus monkeys were studied. INTERVENTIONS: The GnRH antagonist ORG 30850 was administered to long-term ovariectomized monkeys assigned to one of six groups: single subcutaneous injections in group A (n = 4), 0.3 mg/kg; group B (n = 4), 1.0 mg/kg; and group C (n = 3), 3.0 mg/kg; and six consecutive daily subcutaneous injections in group D (n = 2), 0.3 mg/kg; group E (n = 2), 1.0 mg/kg; and group F (n = 2), 3.0 mg/kg. Blood samples were collected daily from 10 days before treatment until 22 days after treatment, then weekly for 6 additional weeks. Intravenous GnRH stimulation tests (10 micrograms/kg) were performed on the day after vehicle injection (control) and the day after completion of treatment(s), and then at weekly intervals. The main outcome measures were serum levels of LH, FSH, and ORG 30850. RESULTS: Administration of ORG 30850 resulted in suppression (P < .05) of LH and FSH in all treatment groups. Long-term suppression (greater than 2 weeks) was evident in all primates receiving a cumulative dose of at least 1 mg/kg. Paradoxically, the responsiveness of the pituitary to exogenous GnRH was accentuated during the time of maximal tonic LH/FSH suppression. CONCLUSIONS: ORG 30850 is a potent long-acting GnRH antagonist. Furthermore, the present in vivo demonstration of heightened pituitary responsiveness to exogenous GnRH emphasizes the divergent mechanisms of action of GnRH antagonists and GnRH agonists.

Animals↗