ASO Visual Abstract: Impact of Race/Ethnicity and County-Level Vulnerability on Receipt of Surgery Among Older Medicare Beneficiaries Diagnosed with Early Pancreatic Cancer

Annals of Surgical Oncology -     

Ectopic T cell receptor expression causes B cell immunodeficiency in transgenic mice

Mice expressing transgenic T cell receptors (TCR) are used to explore important questions in immunity. However, transgene expression may have unexpected effects. We previously reported a B cell immunodeficiency, comprising decreased B cell numbers and diminished antibody responses, in mice that express a transgenic TCR specific for nicotinic acetylcholine receptor; the mice were generated using cassette vectors designed specifically for transgenic TCR expression [see Kouskoff et al. J. Immunol. Methods 1995. 180: 273-280]. We now show data suggesting that this defect is due to the expression and accumulation of TCR alpha and beta chains inside B cells and induction of an endoplasmic reticulum stress response, causing apoptosis at the pre B-I and later B cell stage. Thus, inappropriate transgene expression can profoundly affect B cells, leading to a previously undescribed mechanism of immunodeficiency.     

Culture and in vitro bromodeoxyuridine-labelling of mouse kidney explants

Summary A method is described for extended mouse renal organ culture and is evaluated for the study of cell proliferation in 1 mm³ explants of renal cortex. Explants were maintained for up to 14 days with cellular viability being sustained at 20% of the original tissue block from day 2. Labelling indices in tuft, capsular and tubular cells ranged from 0 to approximately 20% over the culture period, following in vitro bromodeoxyuridine uptake. This technique offers potential for the study of local effects of inhibitors of proliferation.     

"Could it be asthma?": the impact of a mass media campaign aimed at raising awareness about asthma in Australia

Asthma is a very common chronic illness in Australia; however,unrecognized and undertreated asthma is responsible for muchpreventable morbidity in the community. In 1988, a coalitionof private and public sector agencies was formed to conducta national mass communications program aimed at increasing awarenessabout asthma. This pilot campaign comprised a mailout to allprimary care physicians and a mass media campaign, entitled"Could it be asthma?". The impact of this media-based strategywas assessed using population surveys of 1300 adults beforeand after the campaign. Following the campaign, recall of recentasthma media messages increased from 24 to 49% (P < 0.001)and the proportion who recognized possible asthma symptoms intheir household increased from 3.4 to 5.5% following the campaign.Of those with symptoms, twice as many reported that they visiteda doctor to have their symptoms assessed after the campaign.Knowledge of asthma symptoms was significantly higher followingthe campaign (P < 0.001), after adjustment for age, sex andthe presence of asthma in the respondents family. The campaignappeared to have some success in raising awareness about asthma,and has been followed by the development of a National AsthmaCampaign in Australia focusing on reducing asthma morbidityand improving its management.     

Reconnecting with relational values in highly conflicted separating couples: A narrative therapy-informed relational interviewing teamwork-based supervision approach

This article outlines a new supervision practice of narrative therapy-informed reflecting team-based relational interviewing for a high-conflict stuck case of a separated middle-aged couple. The article demonstrates the supervision method consisting in five parts. First, the supervisor interviews the couples' relationship while the team watches from behind the one-way mirror. Second, the team responds to the interview while the couple and the supervisor witness their conversation. The couple is then invited to respond back to the team. Furthermore, there is a meta-conversation about the supervision in collaboration with the couple. The intervention ends with therapeutic letter writing to the relationship. The couple showed a meaningful shift in their positioning towards a more relational awareness and found valuable ways for continuing their therapy. The theoretical elements of the approach underpinning practice to tackle high conflict are considered through the illustration of the case.     

Participation of the Fas-Signaling System in the Initiation of Germ Cell Apoptosis in Young Rat Testes after Exposure to Mono-(2-Ethylhexyl) Phthalate

The Fas-signaling system is composed of the interacting proteins Fas (CD95/APO-1) and Fas ligand (FasL, CD95L, APO-1L) and is proposed to act in the testis as a paracrine signaling mechanism by which FasL-expressing Sertoli cells initiate apoptosis of Fas-bearing germ cells. Here we describe alterations in the expression of Fas and FasL in the testis after the intimate physical association between Sertoli cells and germ cells is disrupted by exposure to the Sertoli cell toxicant mono-2-(ethylhexyl) phthalate (MEHP). Young, 28-day-old Fisher rats were treated with MEHP (2 g/kg po) and killed 0, 3, 6, and 12 h after exposure. Immunohistochemical analyses revealed a significant increase in the numbers of Fas-positive germ cells as well as increases in the expression of Sertoli cell FasL. Western blot analysis demonstrated a time-dependent increase in the production of the soluble form of FasL after MEHP exposure and suggests that it may participate in triggering apoptosis in germ cells that have lost their intimate association with the Sertoli cells. Measurement of Fas in cytosolic and membrane fractions of testis homogenates by Western blot analysis revealed a significant shift of Fas expression into the membrane fraction after MEHP exposure. Taken together, these observations indicate that the Fas-mediated paracrine signaling mechanism participates in triggering apoptosis of germ cells despite the loss of their close physical association with Sertoli cells. A working model is presented to explain the involvement of the Fas-system in stimulating germ cell apoptosis after MEHP exposure.     

Rotational behaviour and cGMP responses following manipulation of nigral mechanisms with chlordiazepoxide

Summary Unilateral stereotaxic injections of 1 g of the soluble benzodiazepine chlordiazepoxide hydrochloride into the predominantly GABA-containing zona reticulata of the substantia nigra of amphetamine-pretreated rats induced rotational behaviour similar to that seen following unilateral elevation of nigral GABA levels and amphetamine treatment; this effect was not seen following injections into the vicinity of the predominantly dopamine-containing zona compacta. Chlordiazepoxide-induced rotations were abolished by the GABA-antagonist picrotoxin. Both chlordiazepoxide and GABA depressed production of cyclic 3,5-guanosine monophosphate in samples of nigral tissue in vitro as estimated by radioimmunoassay. It is concluded that chlordiazepoxide may enhance GABA transmission within the substantia nigra, by some as yet unidentified mechanism, to create asymmetric activity in GABA-modulated neurones and hence induce rotation.