<p>The response of the intrapulmonary artery (IPA) to a variety of endogenous lung amines and prostaglandins (PG) was examined to determine if a differential sensitivity to these vasoactive substances existed between segments taken from two sites on the artery. Longitudinal strips of proximal (PIPA) and distal (DIPA) segments of the left lower lobar intrapulmonary artery were taken from rabbit lungs and isometric tension measured during superfusion abt 37°C with physiological saline. Full or partial dose-response curves were obtained for 5-Hydroxytryptamine (5HT), Histamine (HIS), Norepinephrine (NE), Isoproterenol (IsoP), Arachidonic Acid (AA), PGA₁, PGB₁, PGB₂, PGE₁, PGE₂ and PGF₂α. In addition to pharmacological studies, length-tension properties of the segments utilized were examined and a qualitative analysis of smooth muscle content and orientation was undertaken. All prostaglandins elicited contractile effects, of varying magnitudes, at high doses. Prostaglandins A₁, E₁, and E₂ produced little or no contractile responses or slight relaxant activity in unstimulated PIPA and DIPA segments at low doses. 5HT contracted both PIPA and DIPA segments in a dose dependent manner, however, proximal segment maximal effects and sensitivity were significantly greater than those of the distal segment. Both PIPA and DIPA segments contracted to HIS and maximal effects were similar both segments. Mepyramine (10ˉ⁹M) antagonized contractile responses to HIS. In the presence of 10ˉ⁷M mepyramine, HIS produced dose dependent relaxation of precontracted PIPA and DIPA segments. Cimetidine (10ˉ⁵M) antagonized this relaxation indicating that HIS relaxant effects are mediated by H₂-HIS receptor stimulation in both segments. PIPA segments contracted in response to NE while the DIPA segment responded poorly or not at all suggesting a paucity of alpha adrenoreceptors in distal segments. IsoP produced dose dependent relaxation, that was antagonized by propranolol, of precontracted PIPA and DIPA segments. The dose related contractile response to AA was similar in both PIPA and DIPA segments. These studies indicate that regional differences exist in the response of rabbit IPA to some agonists.</p> / Master of Science (MS)

<p>2-Azidoadenosine has previously been shown to be a potent activator of adenylate cyclase in human platelet particulate fractions. In the present study, the activation of adenylate cyclase was enhanced by: (a) reducing Mg²⁺ concentration in the assay mixture, (b) adding excess adenosine deaminase during the incubation, and (c) using rabbit platelets instead of human platelets. Under these optimal conditions a 200% increase in adenylate cyclase activity was achieved with 10 μM 2-azidoadenosine.</p> <p>2-Azidoadenosine was stable in aqueous buffer systems in the absence of light. At pH 7.4, 2-azidoadenosine exists as two tautomers, the azide form and the tetrazole form which were shown to interconvert in a first order fashion with a half-life of 15.3 min at 22°C. These two tautomers appear to be equipotent in their activation of platelet particulate fraction adenylate cyclase. However, on irradiation at 313 nm only the azide form appears to be photolysed to a mixture of products, presumably via a nitrene intermediate.</p> <p>Although the photolysis of 2-azidoadenosine in the presence of platelet particulate fraction produced activation of platelet adenylate cyclase, evidence was obtained that this was not the result of photoaffinity labeling. The individual effects of pre-exposure to 2-azidoadenosine and irradiation at 313 nm were additive.</p> <p>Activation of adenylate cyclase by 2-azidoadenosine added to the enzyme assay was reduced if the particulate fraction had been exposed to UV radiation. The same reduction in activation by 2-azidoadenosine added to the assay was seen when the prior irradiation of the enzyme was carried out in the presence of 2-azidoadenosine.</p> <p>The ³H covalently bound to the platelet particulate fraction upon irradiation in the presence of 2-azido[³H] adenosine was shown to be radiation dependent. However, pre-irradiation of 2-azido-[³H] adenosine generated a product that covalenty labeled platelet particulate fraction as effectively as irradiation of 2-azido[³H]-adenosine in the presence of particulate fraction. This indicates that affinity labeling rather than photoaffinity labeling had occurred. Some inhibition of this labeling was produced by the addition of unlabeled 2-azidoadenosine, 2-chloroadenosine and theophylline. However, neither adenosine nor N⁶-cyclohexyladenosine caused inhibition of labeling when present during photolysis, suggesting that adenosine receptors were not detected. Inhibition of labeling by dipyridamole and coformycin suggested reactions with adenosine transport proteins and adenosine deaminase, respectively. Further studies with various combinations of ligands are required to determine the nature of sites labeled by the photolysis products of 2-azido[³H]adenosine.</p> / Master of Science (MS)

<p>The genetic region which exerts a major influence on graft rejection is known as the major histocompatibility complex or MHC. The MHC in man, the HLA system, includes at least five distinct multi-allelic loci, HLA-A,-B,-C,-D and -DR. The HLA system possesses three fundamental characteristics: it is highly polymorphic; its alleles are in linkage disequilibrium with one another as well as with other loci; and the HLA antigens demonstrate extensive cross-reactivity.</p> <p>A number of previous reports have established associations between certain HLA-B antigens and juvenile-onset insulin-dependent diabetes mellitus (JOD). In this investigation we have studied the distribution of HLA antigens in patients with diabetes mellitus with a special emphasis on HLA antigens belonging to the DR locus. We observed a significant increase in the incidence of HLA-DR4 in JOD patients as compared to its frequency in the normal controls. The present data also confirm earlier reports of the increased incidence of HLA-B15, -B40 and -CW3 in the patient group. Further analyses of the data showed that the primary association of JOD was with HLA-DR4 and the associations with the HLA-B and -C loci antigens were secondary in nature.</p> / Master of Science (MS)

<p>The current method presently in use for diagnosing male asymptomatic urethral gonococcal carrier is considered unsuitable for screening purposes in Sierra Leone. A search for a reliable, cheap, simple, and unobtrusive method found the first voided urine (FVU) as a specimen for culture to be the most promising. Because of methodologic weaknesses associated with previous evaluation of the FVU and the change in the population to which it would be used, blind adoption of the FVU was considered inappropriate.</p> <p>A protocol for validating the FVU in Sierra Leone is presented. The major methodologic problems addressed were definition of asymptomatic male urethral gonococcal carrier, the selection of the study population, and quality control in the laboratory.</p> <p>The finding of a sensitivity of 0.9 or greater for the FVU will be considered valid for the study.</p> / Master of Science (MS)

<p>The effects of liver on pituitary prolactin (PRL) secretion were investigated using an in vitro organ culture system. It was determined that various preparations of liver when coincubated with pituitary tissue resulted in a diminished PRL content in the bathing culture medium. Female Wistar rats (>200gm) provided the source for liver chunks (~150mg) that were coincubated with pituitary tissue obtained from female Wistar rats (>200gm) primed with estradiol-17-β and progesterone. The PRL content of the culture medium obtained from the liver - pituitary coincubate was reduced significantly (p<.001) compared to control. This effect could not be attributed to PRL degradation and/or binding to liver and was therefore interpreted as inhibition of secretion. The effect was partly but not completely antagonized by the addition of Haldol at concentrations ranging up to 1000nM.</p> <p>It was also noted that the diminished PRL content was observed when methanol extracts of male and female livers were coincubated with male and female (primed and unprimed) pituitary tissue. It is concluded that factors associated with liver and extracts of liver inhibit the secretion of prolactin. These factors are thought not to mediate all of their actions through the dopamine receptor as maximally effective concentrations of Haldol only partially eliminate this inhibition.</p> / Master of Science (MS)

<p>Endogenous protein kinase activity was detected on the external cell surface of both normal and Rous sarcoma virus (RSV)-transformed chick embryo fibroblasts (CEF). Cells growing in plastic dishes were incubated with [Υ-³²P]ATP for 20 minutes. Under the conditions employed, only proteins located on the external cell surface were labeled, as the radioactivity could be removed by mild trypsin treatment. In addition, exogenous histones were phosphorylated when added to the reaction mixture. The addition of cAMP and cGMP to the reaction had virtually no effect on ³²P incorporation, suggesting there is little or no cyclic nucleotide-dependent protein kinase activity present on the external cell surface. Cell surface protein kinase activity was higher in RSV-transformed CEF than in normal CEF, and, using a temperature-sensitive src mutant, this difference was found to be transformation-specific. Several differences were observed in the cell surface proteins phosphorylated in normal and transformed cells, and at least two of these were transformation-specific. These data suggest that changes in external cell surface protein phosphorylation are associated with RSV transformation and thus could play a role in the formation of the transformed cell phenotype.</p> / Master of Science (MS)

<p>This thesis intends to study the effects of introducing a pharmacy-service-package in three health districts of the State of Tlaxcala, Mexico. Each district consists of several villages with rural health centres. They have small variation in size and their total economy and natural resources are almost equal. Districts have some features in common, none of them have experienced the "intervention" and all have the same health care system.</p> <p>The investigative method followed consists of randomly allocated intervention and then surveying the districts at two points in time, noting the changes that occur in the interim. Thus it basically requires two sets of observations, one for what might be called the before period (from 1977-1981), the other for what might be called the after period (1982-1983).</p> <p>These districts have already been studied by the University of Mexico. From this survey and auxilliary resources, enough information has been assembled that will be used to determine the initial health care conditions of the districts in the base line period. The investigation of the follow-up and terminal period are the author's responsibility. This work will consist of the designing of a study to collect comparable data and the designing of the analysis to provide evidence of the most important changes that will take place during the study.</p> <p>Chapter One contains an overview of Mexico. Chapter Two describes the current health care system in Mexican rural areas with emphasis on pharmaceutical services. A review of the literature is presented in Chapter Three. In an attempt to establish some basis for the design of a study, existent data is presented in Chapter Four. In this chapter also a proposed protocol presents the design of a definitive study to analyse the effects of pharmacy services in those districts.</p> / Master of Science (MS)

<p>In our investigations concerning the control of synthesis of mouse alpha-1-protease inhibitor (α1Pi), also called alpha-1-antitrypsin (α1AT), a major inhibitor of serum proteases, we had reason to attempt to develop a monoclonal antibody to this molecule to clarify some apparent molecular heterogeneity, as conventional approaches to separate the isoproteins had met with limited success. We immunized Lewi rats with purified mouse α1Pi and fused the immune spleen cells with mouse SP2 plasmacytoma cells after optimizing some of the fusion parameters such as the source of polyethylene glycol (PEG), its concentration and exposure time to cells. In addition, we examined two different fusion protocols for their ability to produce xenogenic rat X mouse hybrid cells. Several hybridomas were produced, one in particular secreting rat IgM specific for mouse α1Pi. Screening of the positive clones was carried out by modified ELISA and radioimmunoassays. Characterization of the cell product was completed by SDS-PAGE and radioimmunoelectrophoresis. Specificity of the secreted immunoglobulin (D7-IgM) was determined using crossed radioimmunoelectrophoresis with ³⁵S-methionine labelled monoclonal antibody. The establishment of a mouse ascitic form of the hybridoma was not successful even after prolonged subcutaneous adaptation of the hybridoma line in ALS treated, bone marrow reconstituted, X-irradiated Balb/c recipients. Mice bearing the solid tumor exhibited pathology in the liver in the form of discrete necrotic lesions suggesting metastatic localization of the hybridoma in the liver and local production and interaction of the monoclonal antibody with the hepatocyte via one of its secreted molecules, alpha-1-protease inhibitor.</p> / Master of Science (MS)

<p>Each year, educational programs, with the responsibility of graduating health professionals, face the dilemma of selecting the most suitable candidates from numerous applicants. Since the number of positions in these classes is limited, the goal underlying the admission procedure is to identify those most likely to succeed.</p> <p>Nursing programs, in particular, have had difficulty in realizing this goal. Despite the use of a variety of selection devices by different schools, the attrition rate of nursing students consistently remains between 30 and 40 percent.</p> <p>The reduction of this attrition rate, by careful examination of various admission methods, will be addressed in this thesis. First, the scientific literature examining attrition and admission procedures in nursing, as well as other disciplines, will be reviewed. Following this, the extent of the attrition problem, specifically in the baccalaureate nursing program at McMaster University, will be explored by means of a retrospective analysis of four years of data. Finally, the design of two randomized controlled trials, each addressing one of two categories of applicants, will be described.</p> <p>The McMaster baccalaureate nursing program presently assesses candidates applying for a position directly upon completion of secondary school on the basis of Grade 13 marks. A second group, 'special' applicants, are considered on the basis of interview scores. The designs will examine two selection devices--the autobiographical letter and the team interview.</p> <p>An additional feature of the proposed study is that all applicants will participate in each admission procedure, but will be blind to the device used to determine their admission. Data about the alternate selection tools will be available for analysis at the end of the study.</p> <p>The validity of the selection devices will be assessed by the examination of four outcome measures. First, success of students in terms of remaining in the program, failing, and withdrawing will be monitored. Second and third, grades in nursing courses for the first two years of the program will be recorded, as well as grades in nursing science courses. Lastly, first and second year tutors will be asked to evaluate the students in terms of their abilities in self-directed learning, problem-solving, interpersonal relations, and self-evaluation.</p> / Master of Science (MS)

<p>Up until the last decade, physicians were content to base management decisions in postoperative surgical patients on the clinical diagnosis of deep vein thrombosis (DVT). Subsequently, multiple studies have demonstrated the insensitivity of clinical diagnosis. Pulmonary embolism (PE) is the most common preventable cause of in-hospital death, which no doubt reflects the insensitivity of clinical diagnosis. Multiple randomized trials indicate that low-dose subcutaneous (sc) heparin and intravenous (IV) dextran are effective for preventing death due to pulmonary embolism in postoperative general surgical patients. Other approaches effective against venous thromboembolism are: intermittent pneumatic leg compression (IPLC) and screening with ¹²⁵I-fibrinogen leg scanning. We have performed a cost-effective analysis in 1,000 patients over the age of forty years undergoing major elective surgery comparing the prophylactic approaches described above with the "no-programme" situation (early ambulation but no other active prophylaxis). The total cost (Canadian dollars) and total effects (deaths from pulmonary embolism averted) are as follows: s.c. heparin $35,714 for 7 lives saved; IPLC $55,803 for 7 lives saved; IV dextran $137,235 for 6 lives saved; leg scanning $396,599 for 7 lives saved; and the "no-programme" situation $53,472 for 8 lives lost. The "no-programme" situation is clearly cost-ineffective. Incremental cost-effectiveness analysis indicates that s.c. heparin is the most cost-effective, followed by IPLC. Dextran and leg scanning, although effective, are both expensive; therefore s.c. heparin or IPLC prophylaxis are preferred.</p> / Master of Science (MS)