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Biomedical subjects

S L Jones

Publications and source records attributed to S L Jones.

At least 91 records · Page 5Linked to original sources

Quantitative structure-activity relationships for estimating the no-observable-effects concentration in fathead minnows (Pimephales promelas).

Quantitative structure-activity relationships, based on hydrophobicity measured as the 1-octanol/water partition coefficient (Kow), have been developed for predicting the acute no-observable-effects concentration (NOEC) for fathead minnows (Pimephales promelas), using a mechanism/mode of action approach. Models were developed for nonpolar narcotics, amine narcotics, polar narcotics, ester narcotics, and respiratory uncouplers. A set of bioreactive chemicals were evaluated, but models based on hydrophobicity alone are inadequate for these chemicals. Additionally, a strong correlation was observed between the acute NOEC and acute lethality measured as the 50% lethal concentration (LC50) for 407 chemicals, regardless of the mechanism/mode of action. This relationship is modeled by the equation log NOEC-1 = 1.007 (log LC50) + 0.246; n = 407, r2 = 0.989, s = 0.142, f = 38095.6, and Pr > f = 0.0001. Examination of the relationship between the acute NOEC and the subchronic NOEC for four mechanisms/modes of action implies that the acute to subchronic ratio is not independent of mechanism of action. The resulting ratios were 6.42 (+/- 3.01) for nonpolar narcosis, 80.00 (+/- 17.78) for polar narcosis, 10.05 (+/- 4.59) for respiratory uncoupling, and 3.94 (+/- 1.72) for bioreactivity.

Animals↗

Repair of cisplatin-DNA adducts by protein extracts from human ovarian carcinoma.

Human ovarian carcinoma exhibits a spectrum of responses to treatment with cisplatin, ranging from marked sensitivity to relative resistance. Variations in the efficiency with which cells repair cisplatin-DNA adducts may in part determine cisplatin sensitivity. We have investigated the use of a novel cell-free assay of nucleotide excision repair of platinated DNA to assess the DNA repair capacity of direct biopsies of untreated human ovarian carcinoma. In this pilot study, ovarian carcinoma extracts performed in vitro excision repair of platinated DNA. Moreover, tumors from different individuals varied as much as 10-fold in their repair capacity in this assay.

Animals↗

Heterogeneous repair of platinum-DNA adducts by protein extracts from mammalian tissues.

Cis-diamminedichloroplatinum (II) (cisplatin) is a mainstay of human cancer chemotherapy. In addition to its antitumour effects however, cisplatin is toxic to normal tissues, causing dose-limiting nephrotoxicity and neurotoxicity. On the other hand, myelosuppression is uncommon. In the light of data suggesting a role for DNA repair mechanisms as determinants of cellular cisplatin sensitivity, we postulated that varying DNA repair capacities between tissues could explain the patterns of organ toxicity seen in clinical practice. Using a novel cell-free assay of repair of cisplatin-DNA adducts, we find that the DNA repair capacity of protein extracts from different tissues varies significantly in our assay, but does not directly correlate with the organ toxicity profile of cisplatin.

Animals↗

Effects of vagal afferent nerve stimulation on noxious heat-evoked Fos-like immunoreactivity in the rat lumbar spinal cord.

Electrophysiological and behavioral studies have described modulation of nociception by vagal afferent fibers. The objectives of this study were to 1) use Fos-like immunoreactivity as a marker for neuronal activity to examine populations of neurons in the spinal cord that are activated by a noxious heat stimulus, 2) determine whether heat-evoked Fos-like immunoreactivity can be modulated by vagal afferent stimulation, and 3) determine whether vagally-mediated effect on heat-evoked Fos-like immunoreactivity can be blocked by intrathecally administered serotoninergic receptor and alpha-adrenergic receptor antagonists. Neurons demonstrating Fos-like immunoreactivity were located in the ipsilateral superficial and deep dorsal horn laminae extending from the caudal L3 through the rostral L6 region of the spinal cord. Stimulation of the right cervical vagus nerve attenuated significantly (42%) heat-evoked Fos-like immunoreactivity in the superficial laminae. The reduction in Fos-like immunoreactivity by vagal stimulation was abolished by intrathecal administration of methysergide, a nonselective serotoninergic receptor antagonist, but not by phentolamine, a nonselective alpha-adrenoceptor antagonist. These results suggest that vagal afferent modulation of spinal nociceptive transmission is mediated, at least in part, by serotonin receptors.

Adrenergic alpha-Antagonists↗

Bromophenacyl bromide binding to the actin-bundling protein l-plastin inhibits inositol trisphosphate-independent increase in Ca2+ in human neutrophils.

Ligation of IgG Fc receptors on polymorphonuclear leukocytes causes an increase in the concentration of free intracytoplasmic Ca2+ ([Ca2+]i) which arises from release of intracellular stores but is independent of inositol 1,4,5-trisphosphate. We found that bromophenacyl bromide (BPB), an alkylating agent which inhibits leukocyte degranulation, adherence, and phagocytosis, inhibited IgG-stimulated increases in [Ca2+]i with an IC50 of 0.2 microM. In contrast, BPB had no effect on inositol 1,4,5-trisphosphate-dependent [Ca2+]i increases induced by fMet-Leu-Phe, complement fragment C5a, ATP, or platelet-activating factor. Using a monoclonal antibody specific for BPB, we identified in polymorphonuclear leukocytes a single cytosolic protein of 66 kDa and isoelectric point pH 5.6 which bound BPB when intact cells were treated with the alkylating agent. This BPB-binding protein was identified as l-plastin, a Ca(2+)-regulated actin-bundling protein. l-Plastin was found associated with the Triton X-100-insoluble cytoskeleton in polymorphonuclear leukocytes adherent to immune complexes, suggesting that BPB affects Fc receptor-mediated signal transduction by altering the actin cytoskeleton. Consistent with this hypothesis, both cytochalasin B and cytochalasin D inhibited the IgG-dependent increase in [Ca2+]i, without any effect on fMet-Leu-Phe-induced Ca2+ release. These data suggest that the actin cytoskeleton is essential for signal transduction from plasma membrane Fc receptors and that l-plastin has a critical role in activation of this pathway.

Acetophenones↗

Renal dysplasia and benign ureteropelvic polyps associated with hydronephrosis in a foal.

A 4-month-old male Trakehner foal with a history of hematuria, poor growth, and abnormal hair was found to have unilateral hydronephrosis and hydroureter, as determined by ultrasonography and surgical exploration. Nephrectomy and ureterectomy were performed as treatment. Gross examination of the ureter and kidney revealed renal pelvic and ureteral polyps causing obstruction and subsequent hydronephrosis. The histologic features were consistent with renal dysplasia. The polyps and renal dysplasia were likely to be congenital, but the etiopathogenesis is not known. The finding that urinary outflow obstruction can disrupt nephrogenesis and lead to renal dysplasia supports the view that the polyps developed, blocked urine flow, and caused the hydronephrosis and renal dysplasia in the foal.

Animals↗

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Adult↗

The Queen's Medical Center Honolulu, Hawaii.

The Queen's Medical Center created and almost fully realized a vision of professional nursing practice. This vision was mission-driven and philosophically oriented in that our Hawaiian heritage and commitment to a patient-centered focus dictated the direction taken. Utilizing the nursing process, we listened to our patients in identifying the nursing model to best meet their needs: primary nursing. In order to achieve that, the nurse at the bedside had to be empowered to make decisions directly impacting patient care. We further committed to treating the whole patient and considering complementary therapies. We have established an evaluation baseline and are committed to a process that will carry us into the year 2000.

Cultural Characteristics↗

An audit of the insulin tolerance test in adult subjects in an acute investigation unit over one year.

OBJECTIVE: We audited our practice of insulin tolerance testing (ITT) in terms of safety and technical success. We reviewed the results of those tests performed over a 12-month period. By relating peak cortisol response to 0900 h screening cortisol level, we determined whether we could reduce the number of tests performed. DESIGN: The results of all ITTs performed on our unit between 1 January and 31 December 1991 were reviewed. PATIENTS AND MEASUREMENTS: Patients were prescreened by measurement of serum cortisol and thyroxine, and recording of an electrocardiogram. A subnormal serum thyroxine (< 58 nmol/l), 0900 h serum cortisol (< 100 nmol/l) or an abnormal ECG were taken as contraindications to the test. Minimum glucose and maximum cortisol levels were recorded, along with peak GH responses when measured. The peak cortisol response was compared to the screening and basal cortisol levels. RESULTS: A total of 161 tests were performed, 135 of which fulfilled our inclusion criteria. The test was technically successful in all but 5 of these; a significant adverse event occurred in one patient with full recovery after reversal of hypoglycaemia. Thirty-two patients had a suboptimal serum cortisol response to hypoglycaemia: screening cortisol level ranged from 128 to 493 nmol/l and 0900 h serum cortisol measured prior to the ITT from 97 to 431 nmol/l. The lowest level of screening cortisol above which all patients would be expected to achieve the normal peak cortisol of 580 nmol/l or over is therefore 494 nmol/l. If this cut-off level had been adopted, 10 (8%) ITTs need not have been performed if their only purpose had been to assess cortisol reserve. Altering the criterion for the necessary peak cortisol to 500 nmol/l did not affect the number of ITTs required. Our lower limit for testing could not be revised upwards from 100 nmol/l. Adequacy of cortisol reserve did not predict a normal GH response to insulin-induced hypoglycaemia. CONCLUSIONS: When performed in an experienced endocrine unit with adequate supervision, the insulin tolerance test is a safe procedure. According to the current sample, fewer tests would be performed without detriment to patient care if those with a screening cortisol of greater than 500 nmol/l did not proceed to testing, unless the purpose of the test was also to exclude GH deficiency. A lower limit of 100 nmol/l appears reasonable and need not be revised upwards.

Acromegaly↗

Genetic-based and assisted reproductive technology of the 21st century.

The scientific advances of human genetics and assisted reproductive technology are redefining the concepts of health and illness by revealing the mysteries of the human genome and the process of conception, implantation, and diagnostic testing of the human embryo. The effect of these discoveries and their clinical applications will move from the tertiary to primary care arena through the ability to readily screen, diagnose, and treat some disorders and offer cure as the end result for others. In addition, the ethical, legal, and social issues, along with the attendant implications for professional practice, will need to be identified. Only a small portion of nurses have had to address the knowledge and practice issues associated with these advances. "Brave new families" are being created. Perinatal nurses must be prepared to meet the emerging needs of these families through the art and science of nursing.

Female↗

Caregiver burden: who the caregivers are, how they give care, and what bothers them.

The present research describes the association between objective and subjective caregiver burden experienced by families and friends of individuals with chronic mental illness. Although there has been a significant quantity of research conducted about burden and mental illness, the findings have been equivocal because of varying definitions of burden and varying sampling procedures. The present research utilizes a standardized interview instrument for caregivers. Caregivers were named by a stratified random sample of clients who have been certified as severely mentally disabled and have received publicly-funded community mental health services in the state of Ohio during the 1990 fiscal year. Data were collected by the first author and a research assistant during telephone interviews between August 1991 and May 1992. One hundred and eighty-nine caregivers were interviewed. Findings showed that the majority of caregivers are female, white, and aged 50 years or more. Parents comprise the largest group of caregivers and slightly more than one third of clients live with the caregiver. The relationship between caregiver and client is generally described as positive; however, the interviews were conducted during a period when the clients' symptomatology was more under control than previously in the relationship. Caregivers state that the clients need help much more often than they ask for it in all categories of possible help. Considering caregiver burden in relation to caregiver behaviors, time management is a somewhat frequent problem that is very troublesome to the caregiver. Considering client behaviors in relation to caregiver burden, embarrassing behaviors are most troublesome and occur with moderate frequency. The surprise element of these behaviors seems to be the most problematic.

Adolescent↗

Physiological and morphological characteristics of spinal neurons projecting to the parabrachial region of the cat.

Neurons in the lumbosacral, superficial spinal dorsal horn in the cat were recorded extra- and intracellularly, using dorsal root stimulation as a search stimulus. Isolated neurons were tested for antidromic activation from the contra- and ipsilateral parabrachial region. Seventy-one nociceptive-specific neurons, 11 innocuous cooling neurons, and 8 multireceptive neurons were antidromically activated from the lateral parabrachial region. The receptive fields and response properties were typical of other lamina I and lamina II neurons, in that the receptive fields were usually discrete and relatively small, and the responses ranged from sluggish and decrementing to brisk and augmenting with afterdischarge. The conduction velocity to the parabrachial region averaged 3.7 m/sec for the nociceptive-specific neurons, 3.9 m/sec for the innocuous cooling neurons, and 13.5 m/sec for the multireceptive neurons. Intracellularly labeled neurons were mostly medium to large Waldeyer-like neurons in lamina I. Some had axon collaterals that distributed varicosities in laminae I, II, and V. These data indicate that a slowly conducting nociceptive-specific and thermoreceptive pathway exists between the superficial dorsal horn and the parabrachial region at the pontine-midbrain junction.

Afferent Pathways↗

Effect of selective inhibition of thromboxane synthesis on renal function in diabetic nephropathy.

Studies of nondiabetic renal disease suggest that thromboxane may be an important mediator of abnormal renal function. The role of thromboxane in diabetic nephropathy is not fully understood. We measured in a double-blind, randomized, placebo-controlled crossover study the effect of a thromboxane synthase inhibitor (FCE 22178, 400 mg two or three times per day) on urinary excretion of thromboxane B2 and 6-keto-prostaglandin F1 alpha, glomerular filtration rate (measured as clearance of polyfructosan), effective renal plasma flow (clearance of para-aminohippuric acid), fractional clearances of albumin and immunoglobin G and the reabsorption rate of beta 2-microglobulin in 15 patients with type 1 (insulin-dependent) diabetic nephropathy. In seven additional patients, the effect of the thromboxane synthase inhibitor given as 400 mg twice per day was compared with that of the thromboxane synthase inhibitor given as 400 mg three times per day. FCE 22178 administration caused a significant inhibition in the excretion of urinary thromboxane B2 and 2,3-dinor-thromboxane B2 compared with placebo (12.3 +/- 2.1 vs 24.6 +/- 5.1 ng/gm creatinine, p = 0.006, and 78.5 +/- 20.3 vs 335.5 +/- 84.1 ng/gm creatinine, p = 0.004, respectively) without any compensatory increase of 6-keto- prostaglandin F1 alpha or 2,3-dinor-6-keto-prostaglandin F1 alpha that reflect prostacyclin I2 biosynthesis. Glomerular filtration rate, effective renal plasma flow, renal vascular resistance, and filtration fraction were not significantly different after placebo or thromboxane synthase inhibitor treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Clostridium septicum septicemia in a neonatal foal with hemorrhagic enteritis.

Clostridium septicum was isolated by anaerobic culture of blood collected from a 3-day-old foal with hemorrhagic enteritis and signs suggestive of septicemia. The foal responded well to treatment with intravenous fluids, antibiotics, plasma, and oral gastrointestinal protectants. One month after apparent complete recovery from the septicemia and hemorrhagic enteritis, the foal was euthanized during an acute episode of colic that was caused by severe, strangulating intestinal adhesions, thought to have formed as a result of peritonitis secondary to the hemorrhagic enteritis. The value of anaerobic culture of blood in foals with signs suggestive of septicemia is emphasized by the case presented here, as is the importance of evaluating the presence and extent of peritoneal inflammation in foals with hemorrhagic enteritis. To our knowledge, Clostridium septicum has not previously been reported to cause septicemia in neonatal foals.

Animals↗