Predictors of psychosocial distress 12 months after diagnosis with early and advanced prostate cancer.

OBJECTIVE: To assess psychosocial distress in patients with early (localised) and advanced (metastatic) prostate cancer (PCA) at diagnosis (Time 1) and 12 months later (Time 2), and identify psychosocial factors predictive of later distress. DESIGN, PARTICIPANTS AND SETTING: Observational, prospective study of 367 men with early (211) or advanced (156) PCA recruited as consecutive attendees at clinics at seven public hospitals and practices in metropolitan Melbourne between 1 April 2001 and 30 December 2005. Both groups completed questionnaires at Time 1 and Time 2. MAIN OUTCOME MEASURES: Health-related quality of life as assessed by the Short Form 36-item Health Survey; psychological distress, including depression and anxiety as assessed by the Brief Symptom Inventory; and coping patterns as assessed by the Mini-Mental Adjustment to Cancer scale. RESULTS: Over the 12 months, both the early and advanced PCA group showed reduced vitality and increased depression and anxiety; this effect was greater in the advanced PCA group. Mental health, social functioning and role-emotional functioning also deteriorated in the advanced group. Predictors of depression at Time 2 for the early PCA group were depression, vitality and a fatalistic coping pattern at Time 1; anxiety at Time 2 was predicted by anxiety and vitality at Time 1. In the advanced PCA group, depression at Time 2 was predicted by depression and mental health at Time 1; anxiety at Time 2 was predicted by anxiety, mental health, cognitive avoidance and lower anxious preoccupation at Time 1. CONCLUSIONS: Men with early PCA experience decreasing vitality and increasing psychological distress over the 12 months following diagnosis; this trend is accelerated after diagnosis with advanced PCA. A fatalistic coping pattern at diagnosis of early PCA predicts later depression while cognitive avoidance and lower anxious preoccupation at diagnosis of advanced PCA predict later anxiety.

Psychosocial adjustment in newly diagnosed prostate cancer.

OBJECTIVE: To examine the psychological and social adjustment of men with early or advanced stage prostate cancer and to compare them with a matched group of cancer-free community volunteers. METHODS: A longitudinal observational study in which 367 men recently diagnosed with early (n=211) or advanced stage (n=156) prostate cancer were compared to 169 cancer-free men from the community, of similar age and residential area, using self-report measures of psychosocial adjustment. RESULTS: On the mental health subscales of the Short-Form 36-item Health Survey, men with advanced disease had lower vitality and social functioning than the other two groups, and lower mental health scores than the comparison group. Both patient groups had lower role-emotional scores than the comparison group. With regard to the Brief Symptom Inventory, the advanced disease group had higher somatization scores, and lower interpersonal sensitivity and paranoid ideation scores than the early stage group and the community comparison group. In terms of psychiatric morbidity, there were higher rates of anxiety disorders but not depressive disorders in both patient groups although overall diagnosis rates were low. No differences were found in terms of couple or family functioning. CONCLUSIONS: There is impairment in psychosocial function in men with prostate cancer, particularly those with advanced disease, but no increase in the rate of formal psychiatric disorder or adverse effects on the couples and families. This suggests directions for psychosocial interventions with these patient groups.

Amino acids critical for binding of autoantibody to an immunodominant conformational epitope of the pyruvate dehydrogenase complex subunit E2: identification by phage display and site-directed mutagenesis.

The E2 subunit of the mitochondrial multienzyme pyruvate dehydrogenase complex (PDC-E2) is the major autoantigen in the liver disease, primary biliary cirrhosis (PBC). An epitope region which has been localized to amino acids 91-227 is believed to include the residue K173 to which is attached the lipoyl cofactor. We investigated structural features of this epitope region by screening random peptide phage-displayed libraries and identified prevalent phagotopes that contained likely contact amino acids in separate regions of the linear sequence, H132M133, and F178, V180. These were confirmed by site-directed alanine mutagenesis singly or in combination of the HM and FV residues in wild-type (wt) PDC-E2, and by immunization of rabbits with phage that expressed peptides MHLNTPP or FVLPWRI. The lipoyl lysine K173 also was mutated. Reactivities of mutants and wild-type (wt) PDC-E2, compared by ELISA using 12 PBC sera, showed decremental reactivity of mutant versus wt PDC-E2 (normalized to 100%): wt PDC-E2 (100%)>>PDC-E2(F178A,V180A) (mean+/-S.D., 59+/-17%)>PDC-E2(M133A) (50+/-13%)>PDC-E2(H132A) (36+/-13%)>PDC-E2(H132A,M133A) (28+/-8%)>PDC-E2(H132A,M133A,F178V,M180A) (18+/-13%). Notably PDC-E2(K173A) retained full reactivity (93+/-21%). Rabbits immunized with phage peptides generated antibodies reactive with entire PDC-E2. Our data convincingly validate phage library technology for defining spatially disparate contact residues for conformational epitopes. Ensuing data could be generally applicable to search for occult extrinsic agents as initiators of autoimmunity.

Two monoclonal antibodies to precisely the same epitope of type II collagen select non-crossreactive phage clones by phage display: implications for autoimmunity and molecular mimicry.

Two monoclonal antibodies (mAb) CB268 and CII-C1 to type II collagen (CII) react with precisely the same conformational epitope constituted by the residues ARGLT on the three chains of the CII triple helix. The antibodies share structural similarity, with most differences in the complementarity determining region 3 of the heavy chain (HCDR3). The fine reactivity of these mAbs was investigated by screening two nonameric phage-displayed random peptide libraries. For each mAb, there were phage clones (phagotopes) that reacted strongly by ELISA only with the selecting mAb, and inhibited binding to CII only for that mAb, not the alternate mAb. Nonetheless, a synthetic peptide RRLPFGSQM corresponding to an insert from a highly reactive CII-C1-selected phagotope, which was unreactive (and non-inhibitory) with CB268, inhibited the reactivity of CB268 with CII. Most phage-displayed peptides contained a motif in the first part of the molecule that consisted of two basic residues adjacent to at least one hydrophobic residue (e.g. RRL or LRR), but the second portion of the peptides differed for the two mAbs. We predict that conserved CDR sequences interact with the basic-basic-hydrophobic motif, whereas non-conserved amino acids in the binding sites (especially HCDR3) interact with unique peptide sequences and limit cross-reactivity. The observation that two mAbs can react identically with a single epitope on one antigen (CII), but show no cross-reactivity when tested against a second (phagotope) indicates that microorganisms could exhibit mimics capable of initiating autoimmunity without this being evident from conventional assays.

A diabetes-related epitope of GAD65: a major diabetes-related conformational epitope on GAD65.

The 65-kDa isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes, and most patients have serum antibodies reactive with conformational epitopes on the GAD65 molecule. The aims of this study were to prepare mutants of GAD65 to further localize the type 1 diabetes epitope in the region of the PEVKEK loop of GAD65 and to identify the particular amino acids within the epitope that are recognized by autoimmune diabetes sera.

Shyness and anxiety as predictors of patterns of Internet usage.

The Internet has the potential to empower or isolate. Shyness and anxiety may potentially influence the extent to which people avail themselves of Internet services such as email, chat rooms, information searches, entertainment, and commerce. To understand how personality moderates Internet usage, 177 participants completed an Internet Use Survey, the Social Reticence Scale, and a Trait Anxiety Inventory. Shyness, anxiety, gender, and academic achievement were employed within separate multiple regressions to predict forms of Internet usage. The use of email and chat-rooms was not related to shyness or anxiety, suggesting that shyness or anxiety does not pose an obstacle to these Internet applications. Males were more likely to use the Internet for downloading entertainment. Shy males were more likely to use the Internet for recreation/leisure searches. Highly educated males were more likely to use the Internet for banking and paying bills. Although shyness or anxiety does not seem to modify the communicative functions of the Internet, it may influence people's use of other recreational applications.