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Biomedical subjects

J A Cook

Publications and source records attributed to J A Cook.

At least 19 recordsLinked to original sources
PubMed1992

Adrenal medullary secretion with splanchnic stimulation in spinal cats.

This project was undertaken to determine whether previously observed adrenal medullary hyperactivity that developed following high spinal cord transection in the cat could be explained by increased sensitivity of the synapse between the splanchnic nerve and chromaffin cell. The splanchnic nerve was stimulated in acute (2-3 h; n = 7) or chronic (61-64 days; n = 7), spinally transected (T3) cats that were decerebrate and unanesthetized. Mean arterial blood pressure and adrenolumbar venous blood flow were significantly greater in the chronic animals. Stimulation (30 V; 1 ms pulses) was applied at 3 Hz and 30 Hz to deliver the same number of pulses within 3 min. Adrenal medullary secretion (ng/min) of epinephrine (EPI), norepinephrine (NE), dopamine, neuropeptide Y (NPY), [Met]enkephalin (ENK), and encrypted [Met]enkephalin was determined at baseline and in relation to both patterns of stimulation. With near threshold (3 Hz) stimulation, the following differences were observed between groups: (1) secretion of EPI, NPY, and ENK was significantly greater in the chronic than in the acute animals; and (2) preferential secretion of NE was elicited in the acute animals. These observations suggest that there may be some facilitation of the splanchnic nerve--chromaffin cell synapse that occurs over time following high thoracic spinal cord transection. However, it is likely that central, spinal mechanisms also contribute to adrenal medullary hyperactivity.

Adrenal Medulla↗
PubMed1992

Measurement of thymidine replacement in patients with high grade gliomas, head and neck tumors, and high grade sarcomas after continuous intravenous infusions of 5-iododeoxyuridine.

Based upon the radiation sensitization properties of the halogenated pyrimidines, 5-iododeoxyuridine (IdUrd) and 5-bromodeoxyuridine, long term i.v. infusions of halogenated pyrimidines in conjunction with fractionated radiation therapy have been evaluated in the treatment of a variety of human malignancies. While clinical studies have attempted to measure the halogenated pyrimidine incorporation, few have successfully related tumor response to the incorporation of IdUrd by the tumor. The present study reports the continuous IdUrd labeling index (number of cells labeled) and the IdUrd corrected replacement (percentage of thymidine replacement in the labeled cells of the population) from the tumors of 17 patients who received continuous infusions of IdUrd (1000 mg/m2/24 h). The tumors treated included four high grade gliomas, five head and neck tumors, four high grade sarcomas, and five other tumors of varying types. Less than 25% of the cells in three of four gliomas incorporated IdUrd after 5-7-day IdUrd infusion time. Corrected replacement for the gliomas ranged from 0 to 4%. In contrast, 63-85% of the cells in the head and neck biopsies were labeled with IdUrd after 3-7-day IdUrd infusions suggesting that these large tumors (3-12 cm diameter) have a high fraction of dividing cells. Corrected replacements values for the head and neck tumor patients ranged from 2.9 to 26.3%. The high grade sarcomas also demonstrated a high percentage of IdUrd labeled cells (57-79%) with three patients having corrected replacements of 7.5-14.2%. The continuous labeling and thymidine replacement data for four patients from whom serial biopsies were taken during IdUrd infusion demonstrated both an increasing IdUrd replacement and continuous labeling index with an increasing duration of IdUrd infusion. The clinical response of both the high grade glioma and head and neck tumor patients indicate that the IdUrd replacement and labeling data may provide some important predictive information with regard to the successful use of the halogenated pyrimidines in clinical radiation trials.

Animals↗
PubMed1992

Determination of cicletanine in human plasma by high-performance liquid chromatography using automated column switching.

The automated determination of cicletanine in human plasma by column-switching high-performance liquid chromatography with fluorescence detection is described. A linear response was observed for the plasma calibration curve in the range 0.05-10 micrograms base/ml. The minimum quantifiable level of the assay was 0.05 micrograms base/ml plasma. The extraction efficiency was approximately 98% for both cicletanine and the internal standard. Precision (coefficient of variation) ranged from 0.9 to 6.3% and the accuracy ranged from -8.5 to 5.3%. Freezing samples up to three months had no apparent effect on sample integrity. The method has been used to analyze rat and dog plasma samples from toxicology studies as well as human plasma from phase I and II clinical trials. This method has several advantages over previously published methods including reduced sample volume requirement and minimal sample preparation.

Animals↗
PubMed1992

Marital satisfaction among parents of the severely mentally ill living in the community.

Factors influencing marital satisfaction among 131 parents of adult offspring with severe mental illness were explored. Those found to be most predictive of marital satisfaction were parents' ability to comfort one another, parents' gender, number of offspring, family income, and interpersonal sensitivity. Implications of these findings for practical and policy approaches to preventive intervention are discussed.

Adaptation, Psychological↗
PubMed1992

Intranasal splints and their effects on intranasal adhesions and septal stability.

Intranasal splints have been used to maintain septal stability and prevent intranasal adhesions following septal surgery. However, their efficacy and attendant morbidity have received surprisingly little attention. Our prospective study of 100 adults was divided into patients undergoing septoplasty or submucous resection of the nasal septum alone (n = 50) and those undergoing combined septal and inferior turbinate surgery (n = 50). All patients were randomized to have paired silicon rubber splints inserted for 7 days or not at all. All noses were additionally packed with 2 pieces of Jelonet for 12-20 h and examined and cleaned at 1 and 6 weeks post-operatively. The position of the septum, patency of the airways, presence of adhesions and degree of discomfort were recorded. Statistical analysis of the 89 complete sets of results obtained indicated splints added significantly to post-operative discomfort in both groups, with no demonstrable benefit to the patient.

Adolescent↗
PubMed1992

A randomized comparison of three post-tonsillectomy diets.

Traditionally, soft cold foods have been recommended after tonsillectomy to aid comfort and haemostasis but, more recently, rougher foods have been advocated to promote physiologically normal deglutition. This trial was designed to discover whether post-tonsillectomy dietary advice has any influence on recovery. 150 patients due to undergo tonsillectomy were prospectively randomized to 1 of 3 diets: mainly rough food, mainly soft food, and no advice except to eat regularly. Food consumption, analgesia intake and pain levels were recorded daily by each patient. Tonsillar fossa slough and secondary haemorrhage were evaluated 1 and 2 weeks after surgery. Results of 137 patients were obtained. There were no significant differences between the diets regarding post-operative pain, analgesic required, healing rates or secondary haemorrhage. Specific post-tonsillectomy dietary advice need not be given, other than to encourage regular eating.

Adolescent↗
PubMed1992

Manipulation of the fractured nose under local anaesthesia.

Simple fractures of the nasal pyramid without significant septal deformity may be reduced as effectively under local as under general anaesthesia. Currently, the former may involve regional nerve blockade by intranasal infiltration and is often unpleasant. We have attempted to find a more acceptable method. Fifty consecutive, adult patients with clinically displaced nasal fractures were randomized to receive either blocks of the infraorbital, infratrochlear and external nasal nerves by intranasal infiltration or generalized infiltration of the nasal dorsum by an external route. All patients received intranasal cocaine. Following manipulation, each patient recorded their overall discomfort level and subjective nasal airway patency. The surgeon recorded the cosmetic result. Analysis revealed the internal route to be significantly more painful (P less than 0.001) and with no advantage to the patient with respect to post-operative airway patency or cosmesis. We recommend the technically easier external method for this procedure.

Adult↗
PubMed1992

Treatment of T3 carcinoma of the larynx by surgery or radiotherapy.

T3 carcinoma of the larynx may be treated by surgery or by irradiation. A large number of oncologists feel that radical surgery offers a better chance of cure than does radiotherapy. We report a series of 147 patients with T3 N0 carcinoma of the larynx treated either by irradiation with salvage laryngectomy in the event of a recurrence, or by total laryngectomy. 109 patients had radiotherapy and 38 patients underwent surgery. The groups were well matched with no significant difference between the significant prognostic factors. The 5-year survival rate between the radiotherapy (70%) and surgery (40%) groups was significantly different (chi 2 = 4.48, d.f. = 1, P < 0.05). In spite of the well known problems associated with retrospective studies the present series suggests that radiotherapy combined with salvage surgery is an oncologically sound option for treating T3 laryngeal carcinoma.

Female↗
PubMed1992

Endotoxin tolerance is associated with altered GTP-binding protein function.

Previous studies have suggested that guanine nucleotide regulatory (G) proteins modulate endotoxin-stimulated peritoneal macrophage arachidonic acid (AA) metabolism. Endotoxin-stimulated metabolism of AA by peritoneal macrophages is decreased in endotoxin tolerance (Rogers et al. Prostaglandins 31: 639-650, 1986). These observations led to a study of G protein function and AA metabolism by peritoneal macrophages in endotoxin tolerance. Endotoxin tolerance was induced by the administration of sublethal doses of endotoxin. AA metabolism was assessed by measurement of thromboxane B2 (TxB2), a cyclooxygenase metabolite. NaF (5 mM), an activator of G proteins, significantly stimulated TxB2 synthesis in control macrophages from 7.7 +/- 0.2 to 19.1 +/- 0.6 (SE) ng/ml (P less than 0.05) at 2 h and was partially inhibited by pertussis toxin, suggesting a G protein-dependent mechanism. Salmonella enteritidis endotoxin (50 micrograms/ml) stimulated a similar increase in TxB2 levels (23 +/- 0.4 ng/ml, P less than 0.05). In contrast to control macrophages, macrophages from endotoxin-tolerant rats stimulated with either NaF or S. enteritidis endotoxin had TxB2 levels that were only 30 and 2% of the respective stimulated control cells. Basal guanosine-triphosphatase (GTPase) activity (33 +/- 6 pmol.mg-1.min-1) in endotoxin-tolerant macrophage membranes was significantly lower (P less than 0.05) than control basal activity (158 +/- 5 pmol.mg-1.min-1). This suppression of macrophage GTPase activity was apparent 48 h after the first in vivo sublethal endotoxin injection (100 micrograms/kg ip). The reduced GTPase activity paralleled in vitro cellular hyporesponsiveness to endotoxin-stimulated TxB2 production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Catalytic hydrogenolysis of poly-iodinated recombinant human insulin-like growth factor II (IGF-II): a potentially useful method for the tritiation of IGF-II.

A method has been developed to prepare, purify, and fully characterize poly-iodinated insulin-like growth factor II (IGF-II) which can then be catalytically deiodinated to produce IGF-II with its native disulfide bonded structure. This method can potentially be adapted to prepare tritiated IGF-II with the use of tritium gas in the hydrogenolysis step. IGF-II was iodinated at all three tyrosines using lactoperoxidase with a three-fold excess of sodium iodide. The iodinated products were purified using reversed-phase HPLC and characterized by peptide mapping. The tyrosine-containing peptides generated by pepsin digestion were characterized by amino acid sequence analysis. Mono- and di-iodinated phenylthiohydantoin tyrosine derivatives were synthesized and used to identify the iodination state of the modified tyrosine residues in the sequence analysis. Purified poly-iodinated IGF-II was deiodinated by hydrogenolysis, over a prereduced palladium (II) oxide catalyst to form IGF-II with its native disulfide bonds intact, as shown by peptide mapping.

Amino Acid Sequence↗
PubMed1991

Determination of a novel steroidal androgen receptor antagonist (Win 49596) in human plasma using solid-phase extraction and high-performance liquid chromatography with ultraviolet detection.

A rapid, sensitive and selective method was developed for the determination of a novel steroidal androgen receptor antagonist (Win 49596, I) in human plasma. The procedure involved extraction from plasma using a solid-phase phenyl support and elution directly onto a reversed-phase C8 column using a mobile phase consisting of 0.2 mol/l sodium acetate buffer at pH 7-acetonitrile (45:55, v/v). Drug was monitored by ultraviolet detection at a wavelength of 238 nm. Linear responses were observed for standards over the range 0.01-5.0 micrograms/ml. The minimum quantifiable level was 0.02 microgram/ml, using a 0.5-ml plasma sample. The precision was 5.5% and the accuracy ranged from -9.4% to 0.23%. The analytical method has been used to quantify I in plasma from dogs and rats and is projected for use with human plasma from clinical trials.

Androgen Antagonists↗
PubMed1991

Endotoxin-induced arachidonic acid metabolism requires de novo protein synthesis and protein kinase C activation.

The mechanisms whereby bacterial endotoxins stimulate arachidonic acid metabolism in macrophages are uncertain. Both protein kinase C activation and de novo protein synthesis occur in macrophages in response to endotoxin. In this study we evaluated the time course and role of protein kinase C and de novo protein synthesis in endotoxin stimulated arachidonic acid metabolism in resident rat peritoneal macrophages. Thromboxane (TX) B2 was measured as the representative arachidonic acid metabolite synthesized in response to Salmonella enteritidis endotoxin, calcium ionophore A23187, or phorbol 12-myristate 13-acetate (PMA). The effect of inhibition of protein kinase C by 1-(5-isoquinolinsulfonyl)-2-methylpiperazine dihydrochloride (H-7) and staurosporine on endotoxin- and A23187-induced TXB2 synthesis was examined. The potential roles of transcriptional and translational events in endotoxin- and A23187-stimulated TXB2 synthesis were determined by utilizing the transcriptional inhibitors camptothecin (10 microM) or actinomycin D (0.08 microM), and the translational inhibitor cycloheximide (0.1 microM). Whereas, A23187 stimulated maximal TXB2 synthesis within 15 min, endotoxin showed a more prolonged time course with a 12-fold increase in TXB2 synthesis above basal levels after 3 h (P less than 0.05). PMA induced an approx. 8-fold increase above basal TXB2 levels that was blocked by inhibition of transcription with actinomycin D. H-7 (10 microM to 50 microM) inhibited endotoxin- and A23187-stimulated eicosanoid synthesis. Staurosporine (0.2 microM) produced a selective 66% inhibition of endotoxin, but not A23187-stimulated TXB2 synthesis. Endotoxin-induced TXB2 production was significantly (P less than 0.05) inhibited by staurosporine, camptothecin, actinomycin D or cycloheximide at intervals from 30 min prior to, through 60 min after endotoxin stimulation. These studies suggest a role for protein kinase C activation and de novo protein synthesis in endotoxin signal transduction events leading to increased macrophage arachidonic acid metabolism. These intracellular events are essential in sustaining the prolonged inflammatory response to endotoxin.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Cellular glutathione and thiol measurements from surgically resected human lung tumor and normal lung tissue.

Cellular glutathione (GSH) levels were measured from 27 human lung tumor biopsies, enzymatically disaggregated, and compared with cells isolated from normal lung of the same patients. GSH levels from normal lung were similar among patients with a mean value of 11.20 +/- 0.58 (SEM) nmol GSH/mg protein (24 patients) with a range from 6.1 to 17.5 nmol GSH/mg protein. GSH levels varied considerably within and across histological tumor types with the following values: adenocarcinomas, 8.83 +/- 0.96 nmol/mg protein (8 patients); large cell carcinomas, 8.25 +/- 2.51 nmol/mg protein (3 patients); and squamous cell carcinomas, 23.25 +/- 5.99 nmol/mg protein (8 patients). The cyclic GSH reductase assay gave only average GSH values and could not distinguish possible GSH variation among subpopulations of cells isolated. Cell volume measurements and microscopic evaluation of cells isolated from both tumors and normal lung revealed heterogeneity with respect to cell types present. To determine the extent of thiol variation among tumor cell subpopulations, tumor cell suspensions were stained with the thiol-specific stain, monochlorobimane (MCB). The accuracy of MCB staining was tested by flow cytometric analysis of 12 in vitro human tumor cell lines and 3 rodent cell lines. A linear relationship was found between the bimane cellular fluorescence and the cyclic GSH reductase assay for cell lines having less than 80 nmol GSH/mg protein (R2 = 0.82). Above 80 nmol GSH/mg protein the rate of change of the bimane fluorescence intensity with respect to increasing GSH concentrations was much reduced. However, by labeling cells with MCB it was possible to distinguish between cell lines with low versus high GSH content. MCB staining of tumor samples revealed multiple populations of cells with respect to thiol levels. In particular, 2 of 8 squamous cell carcinomas had a proportion of cells with elevated fluorescence intensities (from 10 to 35% of the population) suggesting the presence of cells with greatly elevated thiol levels. These findings underscore the complexity of quantitating intracellular GSH levels from tumor biopsies. The combined use of MCB with flow cytometry and conventional GSH assays may help to delineate subpopulations of cells within tumors with different thiol levels.

Adenocarcinoma↗