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Biomedical subjects

K Quinn

Publications and source records attributed to K Quinn.

At least 37 records · Page 2Linked to original sources
PubMed1995

Non-radioactive localization of nucleic acids by direct in situ PCR and in situ RT-PCR in paraffin-embedded sections.

Technological developments have made possible extension of polymerase chain reaction (PCR) analysis to individual cells to localize DNA/RNA with non-radioactive labels at the light microscopic level. This approach, in situ PCR, is particularly useful in resolving low-frequency message expression in mixed populations of cells and tissues. We have established a working protocol for direct in situ PCR and have utilized several controls to validate our results. In this report we outline the procedures for detecting either DNA or RNA in a rapid and reproducible manner. We evaluate the sequential steps required for this analysis, such as protease hydrolysis, DNAse digestion, "hot start" capabilities, and detection methods. We have applied these methods in several applications, including detection of the p53 gene in human tumor samples, localization of insulin-like growth factor-IA mRNA in cell lines with low levels of expression, and distribution of transferrin mRNA in lung cancer cell lines and tumors. We demonstrate from this study that the in situ PCR technique is an investigative approach capable of detecting specific DNA/RNA sequences at the cellular level and of identifying cells with low levels of mRNA expression.

Base Sequence↗
PubMed1994

The role of the insulin-like growth factor I receptor in the transformation by simian virus 40 T antigen.

Balb/c 3T3 cells transformed by the tsA58 temperature-sensitive (ts) mutant of SV40 large T antigen, BalbA58 cells, grow in 1% serum at the permissive temperature of 34 degrees C but fail to grow at the restrictive temperature of 39.6 degrees C. Although incapable of growing, BalbA58 cells, in low serum at 39.6 degrees C, still synthesize DNA and tend to accumulate in the G2 phase of the cell cycle. Growth in 1% serum at 39.6 degrees C resumes if BalbA58 cells are treated with insulin-like growth factor I (IGF-I). By using cells overexpressing the IGF-I receptor, and cells with a targeted disruption of the IGF-I receptor genes, we show that: 1) the activation of the IGP-I receptor by its ligand(s) plays a major role in the ability of the SV40 large T antigen to promote growth in low serum; and 2) the IGF-I receptor plays a role in the progression of cells not only through G1, but also through the S and G2 phases of the cell cycle. These findings, together with other recent findings from the literature, suggest that one of the mechanisms by which oncogenes and tumor suppressor genes regulate cell growth is through the modulation of growth factors and their receptors.

3T3 Cells↗
PubMed1993

Scientific basis for cancer prevention. Intermediate cancer markers.

Promising cancer clinical trials results involving the disruption of early stages of cancer with intervention agents such as tamoxifen or retinoids have led to significant new research interest in developing preventative strategy for the control of epithelial cancers. Key to the efficient progress in this field is a clear understanding of the complex biology of the early stages of cancerization that proceed on the epithelial surface. Systematic analysis of the biology of strategic targets such as growth factors is one approach to this problem. Gastrin-releasing peptide is an autocrine growth factor for certain types of lung cancer cells. Mechanisms involved in the production and activation of this peptide are discussed as an example of how rational approaches to neutralization of cancer promotion biology can be achieved. The tools to monitor the success of this type of intervention also emerge from the understanding of the biology of growth factors, and intermediate end point markers that determine the presence or effects of a growth factor are attractive candidates for evaluation. Additional biologic tools reflecting the early stages of the cancer process need to be validated for use in serially evaluating the status of the relevant epithelium so that the ongoing success of a cancer intervention procedure can be established. Through this type of translational research, important applications of molecular biology may greatly improve the success of preventative strategies for cancer control.

Anticarcinogenic Agents↗
PubMed1993

A support group for people bereaved through suicide.

Although much research has been performed in recent years on the prevention of suicide, less attention has been focused on helping the persons left behind. This article outlines the history of establishing a support group for people who have been bereaved through suicide in an Australian city. It describes the difficulties in establishing the group, its structure, management, and helping functions, and the experiences gained from the initial 7 years of operation. The article has been written in response to requests from medical, social, and lay agencies for information in establishing similar support groups.

Adaptation, Psychological↗
PubMed1993

Morphine elimination and hepatic blood flow--a study in patients with portal hypertension.

To investigate the influence of changes in portal venous blood flow on the clearance of morphine, the elimination of a single intravenous dose of morphine sulphate was studied in twelve patients with periportal fibrosis undergoing distal splenorenal shunt for portal hypertension. All patients had almost normal preoperative liver function. Six patients (Group A) received morphine after induction of anesthesia but before surgery; a further six patients (Group B) received morphine after completion of the splenorenal shunt and removal of all vascular clamps. Blood was sampled for 24 hours after morphine administration and analysed for plasma morphine concentration using high performance liquid chromatography. The maximum concentration of morphine was significantly greater in those patients in Group B who received morphine after the shunt (P < .002). Clearance of morphine during the operation was also significantly reduced in these patients compared with the initial clearance (before release of the clamps) in Group A (P < .004). As a consequence of these changes the AUC was greater in this group (P < 0.004). However, there were no differences with the elimination rates after surgery had finished. The results suggest that in individuals with normal liver function, the clearance of morphine is dependent on hepatic blood flow.

Adult↗
PubMed1992

A population-wide profile of prescription drug use in Saskatchewan, 1989.

OBJECTIVE: To measure the prevalence of prescription drug use in Saskatchewan in 1989. DESIGN: Retrospective study. PARTICIPANTS: A total of 961,203 Saskatchewan residents (including those who died or were born during the study year) who were eligible for coverage under the Saskatchewan Prescription Drug Plan. The study population represented 94% of the province's total population; those excluded were mostly status Indians (for whom a federal plan is available). MAIN RESULTS: At least one prescription was received by 66.0% of the study population in 1989. The mean number of prescriptions per patient was 8.2, and the mean cost of drug material per prescription was $13.95. Females received substantially more prescriptions than males; the difference was particularly notable for cardiovascular agents, antidepressants and benzodiazepines. In the senior population 80.8% received at least one prescription; the mean number of prescriptions per patient was 18.4. The most commonly dispensed drug for the entire study population was amoxicillin (290 prescriptions per 1000 people); triazolam was the most frequently dispensed central nervous system drug (74 prescriptions per 1000 people). Regional variation in overall drug use was remarkably small, although it increased at the drug-class level, especially for tranquillizers. The use of cardiovascular drugs was 27% to 32% higher (depending on how use was measured) per Regina resident than per Saskatoon resident. Benzodiazepines were commonly used on a long-term basis, despite recommendations to the contrary. CONCLUSIONS: The results quantify the prevalence of prescription drug use, underscore the importance of careful management of drug therapy by physicians and pharmacists (especially for seniors), illustrate substantial variation in drug therapy strategies and raise questions about utilization of benzodiazepines and cardiovascular drugs.

Age Factors↗
PubMed1992

Candidate biomarkers for application as intermediate end points of lung carcinogenesis.

The need for validated intermediate end point markers to facilitate lung cancer chemointervention research is compelling. Three major classes of lung markers are relevant for this application. Since lung cancer includes four distinct histologies, markers that map degrees of histologic differentiation are important. Many of the markers for squamous differentiation overlap with the candidates for application in the study of head and neck cancer. Production of tissue-specific cell products especially for surfactant or CEA is of interest, because the gene structure is known and many differentiation-related polymorphisms exist. This strategy would be useful for adenomatous type tissue. A second type of marker is the broad group of differentiation markers. The carbohydrate or blood group-like antigens comprise a representative example. Carbohydrate structures are expressed in a specific sequence during fetal processes, and this sequence appears to reverse with the development of a cancer. Retrodifferentiation of specific differentiation markers is the basis of a major effort to effect earlier lung cancer detection using sputum immunocytochemistry. The final class includes markers which affect either positive or negative aspects of growth. Candidates in this area include growth factors or their receptors, or genes that regulate growth. If the intermediate end point marker reflects tumor biology and that biology is in the causal path of tumor progression, serial observation of that parameter should indicate the success of the intervention. In all three of these examples, the clinical material to be analyzed could be sputum specimens, bronchial biopsies or resected lung tissue. Systematic analysis of these markers in context of intervention trials is required to validate their utility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1992

Rational targets for the early detection of lung cancer.

The fact that routinely effective treatments for disseminated lung cancer are not available has prompted the search for effective early detection systems. It is important to identify lung cancer while it is still confined to the bronchial epithelium and is potentially curable with local modalities. We have previously reported on an immunologically based assay to identify antigens expressed on shed bronchial epithelial cells. This assay resulted in a statistically significant correlation of immunostaining with the eventual development of lung cancer 2-4 years prior to routine clinical detection. Attempts to further improve this approach require an understanding of the basis for its success. Based on the work of Hakomori and coworkers, this difucosylated Lewis X structure would be a likely marker of carcinogenic transformation of the bronchial epithelium. In fact, an antibody to this structure was useful for sputum immunocytochemistry analysis for early lung cancer detection. Other carbohydrate structures would also be reasonable markers to evaluate for early detection application, based on the known pattern of expression of these structures in fetal, dysplastic, and neoplastic lung tissue. Another antibody used for sputum immunostaining recognizes a 31-kd protein structure; the antibody is not a known member of a likely class of early detection targets. The reported cases of lung cancer missed by the immunostaining approach included principally adenocarcinoma of the lung, suggesting that the addition of a marker(s) of that type of morphologic differentiation should be considered. Markers to dissect the various forms of lung adenocarcinoma are being characterized and are available for evaluation in early detection applications.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed1991

Reversible renal failure following opioid administration.

A patient who received intravenous papaveretum during and after operation developed anuria and biochemical evidence of impaired renal function in the first 6 hours after surgery. Administration of naloxone 0.4 mg was associated with a sustained improvement in urine output. Mean arterial pressure did not change significantly. The impairment of renal function may have been related to high plasma concentrations of codeine, one of the constituents of papaveretum.

Acute Kidney Injury↗
PubMed1990

Further development of a morphine hydrogel suppository.

1. A sustained release monolithic morphine hydrogel suppository (MHS) was developed and administered to five volunteers. 2. The MHS delivered a mean of 55 mg morphine over 12 h. The mean plasma morphine concentration was 15 ng ml-1 from 2 to 12 h after administration. 3. Plasma morphine concentrations were comparable with those reported for the same dose given orally over the same time period. 4. The morphine hydrogel suppository appears to be an effective means of delivering morphine and may be of value in the management of chronic pain.

Administration, Rectal↗
PubMed1989

Tailoring a commercial radioimmunoassay to the range of levels of progesterone occurring in human serum during controlled ovarian hyperstimulation and following embryo/gamete transfer.

While the Pantex direct P radioimmunoassay is used widely in programs of assisted conception, its sensitivity and range do not encompass the wide range of levels of P in serum of many patients during COH and through the first trimester of pregnancy. The present communication details minor modifications to the proprietary Pantex assay which accommodate these requirements. The nature of the changes does not compromise the performance characteristics or simplicity of the original assay and facilitates precise, accurate, and rapid measurement of serum P between 0.05 and 1280 ng/ml.

Embryo Transfer↗
PubMed1989

Responses of patients to different lots of human menopausal gonadotropins during controlled ovarian hyperstimulation.

Responses of patients treated with different lots of human menopausal gonadotropin (hMG) during controlled ovarian hyperstimulation were analyzed. Levels of luteinizing hormone (LH) in serum varied between groups of patients treated with different hMG lots, serum follicle-stimulating hormone (FSH) levels did not differ. In the analysis of levels of estradiol (E2) in serum of patients pretreated with leuprolide acetate (gonadotropin-releasing hormone analog; GnRH-a), there was an interaction between hMG lot and day of stimulation. E2 levels/follicle also diverged between hMG batches as ovum pick-up approached. Within the groups of patients pretreated with GnRH-a, serum FSH/LH ratios varied between 5 and 20, with a batch x day interaction. Ongoing pregnancy rates in the hMG-treatment groups ranged between 0/24 and 7/33 (21%).

Estradiol↗
PubMed1989

Genetically-restricted effector molecules released by human lymphocytes in response to early pregnancy factor.

The binding of early pregnancy factor (EPF) to lymphocytes stimulates the release of soluble effector molecules. Studies in mice have shown that it is these factors rather than EPF as such which are inhibitory in the T cell-dependent reactions, the adoptive transfer of contact sensitivity and the rosette inhibition test. Two factors have been identified: mEPF-S1 (Mr approximately 15,000) is major histocompatibility complex (MHC)-restricted while mEPF-S2 (Mr approximately 55,000) is restricted to a locus (or loci) outside the MHC. In the present paper, evidence is presented which shows that EPF also induces the release of soluble mediators from human lymphocytes. With the rosette inhibition test two factors have been detected, both of similar size and genetic restriction to those described previously in the mouse. One factor, designated hEPF-S1 (Mr 14-18,000), is human lymphocyte antigen (HLA)-restricted and the other, hEPF-S2 (Mr 50-60,000), appears to be restricted to a locus (or loci) outside the HLA complex.

Chaperonin 10↗
PubMed1989

Extrahepatic morphine metabolism in man during the anhepatic phase of orthotopic liver transplantation.

The primary site for the metabolism of morphine has been the subject of controversy for some time. We studied morphine metabolism during the anhepatic phase of orthotopic liver transplantation in seven adult patients. After injection of morphine 10 mg at the beginning of this phase, the plasma and urinary concentrations of unchanged morphine, morphine-3-glucuronide, morphine-6-glucuronide and normorphine were measured by high pressure liquid chromatography. Small but measurable concentrations of morphine metabolites were found in the plasma and urine whilst there was no functional liver tissue in the body. Morphine metabolism increased markedly when the new donor liver was reperfused. This suggests that, in these patients, the liver is the primary site for metabolism of morphine.

Adult↗
PubMed1989

Gonadotropin and estradiol levels during ovarian stimulation in women treated with leuprolide acetate.

Levels of FSH, LH, and estradiol (E2) were measured in the serum of 209 gonadotropin-releasing hormone analogue-treated women and in 202 control subjects during the final 5 days of ovarian stimulation in our in vitro fertilization program. Levels of FSH and E2 in serum of gonadotropin-releasing hormone analogue-treated subjects significantly exceeded control values during the sampling period, whereas LH levels were significantly lower. Concentrations of E2 in serum of gonadotropin-releasing hormone analogue-treated and control subjects were similar when corrected for differences in numbers of follicles aspirated at oocyte retrieval (mean of 8.9 and 7.2 follicles per subject, respectively). Pregnancy rates by diagnostic ultrasound were 18 and 11%, respectively, a statistically significant difference.

Estradiol↗