A Study Guide for The Soteriological Approach to Christian Doctrine

The study guide is designed to be used with the entire section of Mayer’s book dealing with the soteriological approach. This includes some material in lessons 3 and 5 not included in this reprint. We have included the page numbers of those materials in Mayer (according to the 1961 edition) so that those who have access to the full volume may use it. Furthermore, those questions dealing with these materials are marked with an *. We have attempted to construct these questions in such a way that discussion can take place even if all members of the class do not have access to the complete volume

'The medical gaze and the watchful eye' : the treatment, prevention and epidemiology of venereal diseases in New South Wales c.1901 - 1925

From Federation in 1901 through the first three decades of the twentieth century there was a perceptible shift in modes of rule in New South Wales (NSW) related to the management of venereal diseases. At the beginning of the twentieth century a medicopenal approach was central. By 1925, persuasion and ‘responsibilisation’ were becoming important modes, and young people rather than ‘case-hardened prostitutes' were assessed as being a ‘venereal’ risk. Framing this period were three important legislative developments which informed, and were informed by, these shifts: the NSW Prisoners Detention Act 1909, the NSW Select Committee into the Prevalence of Venereal Diseases 1915 and the NSW Venereal Diseases Act 1918. At its core this thesis is concerned with examining shifting modes of rule. This thesis closely examines each. I suggest that these modes of rule can be viewed through the lens of biopolitics, and following Foucault, deploy the ‘medical gaze’ and the ‘watchful eye’ as constructs to examine the relationship between the government of self, government of others and government of the state. I use the medical gaze to describe not only the individual venereal patient attending a hospital and the body of the patient diagnosed with syphilis and/or gonorrhoea, but most importantly to describe the power relationship between the medical practitioner, the teaching hospital and the patient. I use the watchful eye in a more overarching way to suggest the suite of techniques and apparatus deployed by government to monitor and regulate the venereal body politic, both the populations perceived to be posing a venereal risk, and populations at risk of venereal infection. In relation to the venereal body and the venereal body politic, I analyse three fundamental aspects of the management of venereal diseases: treatment, prevention and epidemiology. Treatment: Over this period, treatment moved from lock institutions to outpatient clinics. Embodied in this change was a widespread institutional ambivalence towards treating venereal patients. I contend that treatment of venereal diseases was painful, prolonged and punitive precisely because of the moral sickness perceived to be at the iv heart of venereal infection. I track this ambivalence to a systemic fear of institutional ‘venerealisation’, which decreased perceptibly across the period. Closely analysing surviving patient records, I argue that in their conduct, venereal patients were often compliant, conscientious and responsible. Prevention: I argue that preventative approaches to venereal diseases became increasingly complex, and operated in three domains – preventative medicine (diagnosis, treatment and vaccination); public health prevention (notification, isolation and disinfection); and prevention education (social purity campaigns and sex hygiene). An emerging plethora of community-based organisations and campaigns began to shift the sites and practices of power. Epidemiology: I suggest that there was a shift from danger to risk in the conceptualisation of venereal diseases. This shift necessitated a focus on factors affecting populations, as opposed to factors affecting individuals. This in turn led to the deployment of various techniques to monitor the conduct of venereal populations. The NSW Venereal Diseases Act 1918 created two important new venereal categories: the ‘notified person’ and the ‘defaulter,’ both of which came to permeate renditions of venereal patients throughout the 20th century

Modification of pharmacokinetic and abuse-related effects of cocaine by human-derived cocaine hydrolase in monkeys

Although substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu- CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu-CocH was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000- fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic studies showed that Albu-CocH (5 mg/kg) had a half-life of 56.6 hours in squirrel monkeys. In these studies, plasma levels of cocaine following i.v. 1 mg/kg cocaine were reduced two hours after administration of Albu-CocH, whereas plasma levels of the cocaine metabolite ecgonine methyl ester were increased. These effects were still evident 72 hrs following Albu-CocH administration. In behavioral experiments in monkeys, pretreatment with 5 mg/kg Albu-CocH dramatically decreased self-administration of a reinforcing dose of i.v. cocaine (30 μg/kg/ injection) for over 24 hours. Pretreatment with 5 mg/kg Albu-CocH also attenuated the reinstatement of extinguished cocaine self-administration by an i.v. priming injection of cocaine (0.1 or 0.3 mg/kg) and, in separate studies, attenuated the discriminative stimulus effects of cocaine. The ability of Albu-CocH to attenuate the abuse-related effects of cocaine in squirrel monkeys indicates that further investigation of BChE mutants as potential treatment for cocaine abuse and toxicity is warranted.This research was supported in part by the Intramural Research Program of the NIH, National Institute on Drug Abuse

Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma

To elucidate the mechanisms underlying chromosomal translocations in diffuse large B cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used Southern blotting to detect legitimate and illegitimate CSR events in tumor samples of the activated B cell–like (ABC), germinal center B cell–like (GCB), and primary mediastinal B cell lymphoma (PMBL) subgroups of DLBCL. The frequency of legitimate CSR was lower in ABC DLBCL than in GCB DLBCL and PMBL. In contrast, ABC DLBCL had a higher frequency of internal deletions within the switch μ (Sμ) region compared with GCB DLBCL and PMBL. ABC DLBCLs also had frequent deletions within Sγ and other illegitimate switch recombinations. Sequence analysis revealed ongoing Sμ deletions within ABC DLBCL tumor clones, which were accompanied by ongoing duplications and activation-induced cytidine deaminase–dependent somatic mutations. Unexpectedly, short fragments derived from multiple chromosomes were interspersed within Sμ in one case. These findings suggest that ABC DLBCLs have abnormalities in the regulation of CSR that could predispose to chromosomal translocations. Accordingly, aberrant switch recombination was responsible for translocations in ABC DLBCLs involving BCL6, MYC, and a novel translocation partner, SPIB

Aneuploidy and chromosomal instability in cancer: a jackpot to chaos

Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) is a form of GIN that involves frequent cytogenetic changes leading to changes in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics of cancer cells, their roles in tumor initiation and progression are unclear. On the one hand, CIN and aneuploidy are known to provide genetic variation to allow cells to adapt in changing environments such as nutrient fluctuations and hypoxia. Patients with constitutive aneuploidies are more susceptible to certain types of cancers, suggesting that changes in chromosome copy number could positively contribute to cancer evolution. On the other hand, chromosomal imbalances have been observed to have detrimental effects on cellular fitness and might trigger cell cycle arrest or apoptosis. Furthermore, mouse models for CIN have led to conflicting results. Taken together these findings suggest that the relationship between CIN, aneuploidy and cancer is more complex than what was previously anticipated. Here we review what is known about this complex ménage à trois, discuss recent evidence suggesting that aneuploidy, CIN and GIN together promote a vicious cycle of genome chaos. Lastly, we propose a working hypothesis to reconcile the conflicting observations regarding the role of aneuploidy and CIN in tumorigenesis

Emergence of rationally designed therapeutic strategies for breast cancer targeting DNA repair mechanisms

Accumulating evidence suggests that many cancers, including BRCA1- and BRCA2-associated breast cancers, are deficient in DNA repair processes. Both hereditary and sporadic breast cancers have been found to have significant downregulation of repair factors. This has provided opportunities to exploit DNA repair deficiencies, whether acquired or inherited. Here, we review efforts to exploit DNA repair deficiencies in tumors, with a focus on breast cancer. A variety of agents, including PARP (poly [ADP-ribose] polymerase) inhibitors, are currently under investigation in clinical trials and available results will be reviewed

Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma

Resistance to chemotherapy in ovarian cancer is poorly understood. Evolutionary models of cancer predict that, following treatment, resistance emerges either because of outgrowth of an intrinsically resistant sub-clone or evolves in residual disease under the selective pressure of treatment. To investigate genetic evolution in high-grade serous (HGS) ovarian cancers, we first analysed cell line series derived from three cases of HGS carcinoma before and after platinum resistance had developed (PEO1, PEO4 and PEO6; PEA1 and PEA2; and PEO14 and PEO23). Analysis with 24-colour fluorescence in situ hybridisation and single nucleotide polymorphism (SNP) array comparative genomic hybridisation (CGH) showed mutually exclusive endoreduplication and loss of heterozygosity events in clones present at different time points in the same individual. This implies that platinum-sensitive and -resistant disease was not linearly related, but shared a common ancestor at an early stage of tumour development. Array CGH analysis of six paired pre- and post-neoadjuvant treatment HGS samples from the CTCR-OV01 clinical study did not show extensive copy number differences, suggesting that one clone was strongly dominant at presentation. These data show that cisplatin resistance in HGS carcinoma develops from pre-existing minor clones but that enrichment for these clones is not apparent during short-term chemotherapy treatment

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]