p53 immunohistochemical staining predicts residual disease after chemoradiation in patients with high-risk rectal cancer

This study was conducted to investigate the value of p53 immunohistochemical staining of pretreatment biopsy specimens in predicting the response of rectal cancer to chemoradiation. The study group comprised 42 patients with high-risk rectal cancer treated between July 1990 and July 1995 with a preoperative chemoradiation regimen of 45 Gy of external-beam irradiation and continuous-infusion 5-fluorouracil followed by surgical resection. p53 immunohistochemical staining was performed on pretreatment biopsy specimens. p53 immunohistochemical staining pattern and standard clinical and pathological parameters were correlated with extent of residual cancer in the surgical specimen. Twenty tumors were positive for p53 on immunohistochemical staining, 19 were negative, and 3 were focally positive. Thirteen patients experienced a complete response to chemoradiation. Aberrant p53 protein accumulation, as measured by immunohistochemical staining, correlated inversely with a complete pathological response to chemoradiation (P = 0.005; correlation coefficient = -0.43) and directly with an increased likelihood of residual cancer in the lymph nodes of surgical specimens (P = 0.02; correlation coefficient = 0.39). p53 immunohistochemical staining of pretreatment biopsy specimens correlates with the extent of residual disease after chemoradiation in patients with high-risk rectal cancer.     

A "feminine" model of vulnerability to depressive symptoms: A longitudinal investigation of middle-aged women.

The authors hypothesized that having traits associated with the female gender role is related to psychological distress in women. Specifically, they investigated the effect of low instrumentality and high expressivity, private self-consciousness, and anger-in on depressive symptoms measured 3 years later in 460 middle-aged women during the menopausal transition and times of stress. Multivariate analyses showed that after adjustment for depressive symptoms and educational level at study entry, depressive symptomatology 3 years later was higher among women who were low in instrumentality and high in self-consciousness at study entry. Women who were self-conscious were the most vulnerable to a subsequent ongoing stressor, and women who tended to suppress angry feelings and who used hormone replacement therapy when they were postmenopausal had more symptomatology than did other women. The study showed that midlife may be problematic for women with certain female gender role traits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Eglin-c prevents monocrotaline-induced ventilatory dysfunction

The present study was carried out to investigate the relationship between elastase and monocrotaline (MCT)-induced ventilatory dysfunction in rats. To accomplish this, we used an elastase inhibitor eglin-c to suppress the activity of endogenous elastase. Thirty-five young Sprague-Dawley rats were randomly divided into six groups: control, MCT, eglin-c(1), eglin-c(2), eglin-c(1) + MCT, and eglin-c(2) + MCT. Rats in the control group received no treatment. Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 wk before the functional test. Each eglin-c(1) rat was intratracheally instilled with eglin-c (9 mg/rat) twice in 1 wk. Each eglin-c(2) rat was intratracheally instilled with eglin-c (9 mg/rat) five times in 1 wk. Both eglin-c + MCT groups were treated with the combination of eglin-c(1) or eglin-c(2) and MCT. In the MCT group, there were significant decreases in dynamic respiratory compliance, maximal expiratory flow rate at 50% total lung capacity, and the slopes of the maximal expiratory flow-%total lung capacity curve and the maximal expiratory flow-static recoil pressure curve. However, in the eglin-c(1) + MCT and eglin-c(2) + MCT groups, all of the above-mentioned MCT-induced changes were prevented. All ventilatory values of the eglin-c(1) and eglin-c(2) groups were not significantly different from those of the control group. These results demonstrate that eglin-c treatment prevents MCT-induced ventilatory dysfunction and suggest that endogenous elastase may play an important role in MCT-induced inflammation-mediated ventilatory abnormality.     

Balance of inflammatory cytokines related to severity and mortality of murine sepsis

We tested the hypothesis that, during sepsis, the balance of pro- and anti-inflammatory cytokines is related to severity and survival. Cecal ligation and puncture (CLP) with a large (18-gauge)-, intermediate (21-gauge)-, or small (26-gauge)-diameter needle, or sham laparotomy, was performed on outbred CD-1 mice. Concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and the anti-inflammatory cytokine IL-10 were measured (by enzyme-linked immunosorbent assay) in serum, peritoneal lavage fluid, and liver and lung samples at 4, 8, 24, 48, and 96 h. As the diameter of the CLP needle decreased, the mortality rate decreased (at 48 h: large, 80%; intermediate, 40%; small, 20%; P < 0.05), the TNF-alpha and IL-6 concentrations decreased, and the time-to-peak TNF-alpha expression increased. In contrast, IL-10 concentration increased compared with baseline (serum at 24 h: large, 2.3-fold +/- 1.6-fold; intermediate, 2.0-fold +/- 0.5-fold; small, 49.9-fold +/- 8.3-fold; P < 0.05). Administration of IL-10 (5 microg, intraperitoneal) prior to CLP decreased mortality (P < 0.001). Administration of polyclonal anti-IL-10 serum prior to CLP (0.5 ml intraperitoneal) had the opposite effect and increased mortality (P < 0.001) and TNF-alpha, IL-6, and TNF-alpha mRNA expression compared with controls. Thus, severe sepsis is associated with a largely unopposed inflammatory response, and a largely unopposed inflammatory response (with anti-IL-10) results in severe sepsis and death. Less severe sepsis is associated with greater anti-inflammatory mediator expression, and greater anti-inflammatory mediator expression (with IL-10) results in less severe sepsis. Thus, the balance of inflammatory mediators is related to the severity and mortality of murine sepsis.     

Transrectal ultrasound in male urethritis

OBJECTIVE: To assess the prevalence of prostatic abnormalities in men with gonococcal and non-gonococcal urethritis using trans-rectal ultrasonic markers. DESIGN: A case control study of patients attending a department of genitourinary medicine with symptoms of urethritis. SETTING: Department of Genitourinary Medicine and Department of Radiology in Manchester Royal Infirmary. RESULTS: A total of 42 patients were recruited to the study: 26 with urethritis and 16 controls. Of the 26 study patients, six were gonococcal, four chlamydial, two mixed gonococcal and chlamydia and nine non specific (no organisms detected). Of the 26 study patients, 16 had abnormal scans (61.5%), eight from the chlamydia group and eight from the non specific group. No abnormalities were found in the gonococcal and mixed group. Of the 16 control patients, five had abnormal scans (31.25%), three of these have had a past history of chlamydial urethritis. CONCLUSION: The prevalence of prostatic abnormalities in patients with non-gonococcal urethritis was significantly higher when compared with controls. The cause of these abnormalities is unclear, but is compatible with inflammatory changes within the gland.     

Dependence of the murine antibody response to an anti-CDR2 VH peptide on immunogen formulation

A peptide corresponding to the second complementarity determining region of the heavy chain (CDR2 VH) from a murine anti-CD4 monoclonal antibody, designated L202, was synthesized by solid phase methodology in a number of different antigenic forms, for the purpose of comparing the effectiveness of different adjuvant-carrier systems in the induction of a murine antibody response against the immunizing peptide and parent antibody molecule. Two of the synthetic constructs contained the palmitoyl and N-palmitoyl-cysteinyl-S-(2,3-palmitoyloxy)-propanediol (PAM3Cys) moieties, respectively, attached to the peptide amino terminus with the immunogen comprising liposomal formulations of each. A third immunogen consisted of the CDR2 VH peptide admixed with the PAM3Cys non-covalently and incorporated into liposomes (PAM3Cys + CDR2 VH). A fourth composition comprised the CDR2 VH peptide conjugated to KLH via the sulfhydryl of an added N terminal cysteine (KLH-CDR2 VH) and injected with Complete Freund's adjuvant (CFA). A fifth immunogen consisted of the CDR2 VH peptide synthesized on an octameric, branched polylysine core as a multiple antigenic peptide (MAP-CDR2 VH) injected in the presence of Freund's adjuvant. Groups of five mice were injected intramuscularly with each of these immunogens and bled at two week intervals. The highest anti-peptide gamma-immunoglobulin (IgG) responses (against uncoupled peptide by ELISA) after 56 days were obtained with mice receiving the PAM3Cys-CDR2 VH peptide. However, when screened against the CDR2 V(H) peptide present as the MAP derivative by ELISA, IgG raised against the cognate MAP-CDR2 peptide was much more reactive than IgG raised against the liposomal PAM3Cys-CDR2 VH immunogen. In either case, IgG raised against the KLH-CDR2VH conjugate was poorly reactive. These differences in reactivity to the two forms of the CDR2 VH peptide by ELISA did not correspond to major differences in reactivities to the intact L202 Ab by ELISA. Although the IgG against the MAP immunogen was slightly more reactive than the other antisera against the l202 Ab, all titers were less than 1:100. These data illustrate some limitations of using anti-peptide responses as indicators of potential reactivity against the native protein, but suggest that alternate formulations including lipoidal peptides are more effective than corresponding KLH-peptide conjugates in eliciting Ab responses against poorly immunogenic epitopes.