Metabolism of the alpha,beta-unsaturated ketones, chalcone and trans-4-phenyl-3-buten-2-one, by rat liver microsomes and estrogenic activity of the metabolites.

When chalcone and trans-4-phenyl-3-buten-2-one (PBO) were incubated with liver microsomes of untreated rats in the presence of NADPH, 4-hydroxychalcone and trans-4-(4-hydroxyphenyl)-3-buten-2-one (4-OH-PBO), respectively, were formed as major metabolites. Two minor metabolites of chalcone, 4'-hydroxychalcone and 2-hydroxychalcone, were also observed. The oxidase activity affording 4-hydroxychalcone was inhibited by SKF 525-A, disulfiram, ketoconazole, and alpha-naphthoflavone. The oxidase activities leading to 4-hydroxychalcone and 4'-hydroxychalcone were enhanced in liver microsomes of 3-methylcholanthrene- and phenobarbital-treated rats, respectively. The activity generating 2-hydroxychalcone was enhanced in liver microsomes of 3-methylcholanthrene- and dexamethasone-treated rats. The oxidation of PBO to 4-OH-PBO was inhibited by SKF 525-A, ketoconazole, disulfiram, and sulfaphenazole. This activity was enhanced in liver microsomes of 3-methylcholanthrene-, acetone- and phenobarbital-treated rats. 4-Hydroxylation, 4'-hydroxylation, and 2-hydroxylation of chalcone were catalyzed by rat recombinant cytochrome P450 1A1, 1A2, and 2C6; by 1A1 and 2C6; and by 1A1 and 3A1, respectively. PBO was oxidized by cytochrome P450 1A1, 1A2, 2C6, and 2E1. Chalcone and PBO were negative in an estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7. However, 4-hydroxychalcone, 2-hydroxychalcone, 4'-hydroxychalcone, and 4-OH-PBO exhibited estrogenic activity.     

A case of immunohistochemical false positive staining caused by incompatibility between a CD4 antibody and an autostainer

Precise immunophenotyping of tumor cells by immunohistochemistry is complementary to morphological examination. It is critical for the correct histopathological diagnosis of lymphomas. In this paper, we report a case of T-cell lymphoma whose histopathological diagnosis was confounded by an immunohistochemical pitfall: a false positive caused by incompatibility between an antibody and an autostainer. In this case, based on CD4 immunohistochemistry of the affected lymph nodes, the T-cell lymphoma was diagnosed as CD4-positive at the onset, while it appeared discordantly to be CD4-negative at the second relapse. We noticed that CD4 antibodies and autostainers of different suppliers (designated as suppliers X and Y) were used in an unqualified combination in immunohistochemistry at the onset: that is, the combination of an antibody supplied by X and an autostainer supplied by Y (designated as X-Y combination) was used at the onset. On the other hand, the Y-Y combination was at the second relapse. At the second relapse, flow cytometry of the affected lymph node showed infiltration of CD4-negative T-cell lymphoma. We reasoned that CD4 immunonegativity obtained by the Y-Y combination at the second relapse was specific, while CD4 immunopositivity by the X-Y combination at the onset was false positive. Immunohistochemical reexamination of the lymph node at the onset proved to be CD4-negative by not only the Y-Y but also X-X combinations, confirming our final diagnosis of nodal relapse of CD4-negative T-cell lymphoma. This case illustrates the importance of using compatible combinations of antibodies and autostainers in diagnostic immunohistochemistry.     

Impact of venous invasion on the efficacy of adjuvant chemotherapy in elderly patients with stage III colorectal cancer

One of the reasons for the underuse of adjuvant chemotherapy in elderly patients with stage III colorectal cancer is a small survival benefit. This retrospective study sought to identify the predictive factors for elderly patients who could obtain a sufficient survival benefit. We reviewed the data of 1354 elderly patients (aged ≥70 years) with stage III colorectal cancer who underwent complete resection between January 1997 and December 2006. The efficacy of adjuvant chemotherapy was assessed, and the risk factors for recurrence were determined. The efficacy of adjuvant chemotherapy was also assessed after stratification for the above-mentioned risk factors for recurrence. There was a tendency for adjuvant chemotherapy to be effective in elderly patients (hazard ratio 0.84; 95% CI 0.70–1.01). Age, tumor location, pathology findings, tumor depth, venous invasion and lymph node metastasis were identified to be independent risk factors for recurrence by univariate and multivariate analyses. Among these factors, adjuvant chemotherapy was much effective in the elderly patients with high venous invasion (v2-3) (hazard ratio 0.69; 95% CI 0.52–0.91). High venous invasion (v2-3) was identified to be a predictive factor for elderly patients with stage III colorectal cancer who gained a sufficient survival benefit.     

Construct validity of 2 measures to assess reasons for antipsychotic discontinuation and continuation from patients' and clinicians' perspectives in a clinical trial

ABSTRACT: BACKGROUND: Little is known about the specific reasons for antipsychotic discontinuation or continuation from patients or clinicians perspectives. This study aimed to assess the construct validity of 2 new measures of the Reasons for Antipsychotic Discontinuation/Continuation (RAD): RAD-I (a structured interview assessing the patients perspective) and RAD-Q (a questionnaire assessing the clinicians perspective). METHODS: Data were used from a 12-week antipsychotic trial of schizophrenia patients in which the RAD was administered at study entry and at study completion (or discontinuation). Construct validity was assessed through comparisons of RAD responses, clinicians responses to a standard patient disposition form identifying reasons for patients study discontinuation, and several standard psychiatric measures. Percent agreement quantified the correspondence between patient and clinician scores. RESULTS: Patients indicating lack of improvement/worsening of positive symptoms as a somewhat to primary reason for medication discontinuation had statistically significantly less improvement in Positive and Negative Syndrome Scale positive score than patients not reporting these as a reason (concurrent validity). Similar results were observed for the RAD negative symptom, functional, social support, and adherence items, whereas the mood and cognitive items were not significantly associated with change scores on standard psychiatric measures. Responses to the RAD were also weakly associated with variables that theoretically should not be related to them (divergent validity). Level of agreement between the clinician- and patient-rated RAD scores was high (60%-100%). CONCLUSIONS: Initial validation of the RAD suggests that the instruments are valid tools for gathering detailed information regarding reasons for antipsychotic discontinuation and continuation from patients and clinicians perspectives.     

Longitudinal changes in the well-being of Japanese caregivers: variations across kin relationships

This study examined how the psychological well-being of Japanese caregivers changed over time; it also examined the variation across kin relationships with care recipients. Three interviews over the course of 30 months were conducted with a representative sample of community-dwelling caregivers of frail elderly persons living in a Tokyo suburb. Latent growth modeling demonstrated that mean levels of both depression and emotional exhaustion worsened over time. Change in emotional exhaustion over time showed significant individual variability, whereas change in depression showed little individual variability. Although wife caregivers tended to experience the worst trajectory of emotional exhaustion, daughters-in-law also showed a similar negative trend. The difference in individuals' well-being trajectories by kinship may be explained partly by differences in care recipients' disabilities.     

Enzyme histochemistry is useful to assess viability of tumor tissue after microwave coagulation therapy (MCT): metastatic adenocarcinoma treated by lateral segmentectomy after MCT

We report on a case of metastatic adenocarcinoma of liver that was removed and examined histochemically after microwave coagulation therapy (MCT). The patient was a 65-year-old woman who had a metastatic tumor in the liver (S3) after high anterior resection due to a rectal adenocarcinoma and received MCT against the tumor. One month after MCT, multiple metastatic tumors were detected by abdominal computed tomography (CT) scan. As it was difficult to control them by MCT alone, we performed lateral segmentectomy. To assess the effects of microwave ablation on cellular viability of metastatic tumor, we used enzyme histochemistry for acid phosphatase (AcP), which is positive in macrophages infiltrating in the tumor. In a part of the ablated area of resected liver, there was remaining neoplastic tissue of which the morphology was maintained in H&E staining. This was found to be microwave-fixed non-viable tissue because no enzyme activity of AcP was detected in the infiltrating macrophages. This case report suggests that enzyme histochemistry was useful to assess the effect of MCT, enabling us to distinguish fixed cells from viable cells.     

Disuse atrophy of the left ventricle in chronically bedridden elderly people.

In the elderly cardiac size and function are determined by their level of physical activity. In this study, we assessed by echocardiography, the anatomic and physiologic changes of the heart in 28 elderly patients who had no cardiac disease and who were chronically bedridden. The data obtained were compared to those obtained from a control group of 38 age and sex matched elderly people whose activities had not been restricted. Chronically bedridden patients had markedly smaller left ventricular dimensions in both end-diastole and end-systole and smaller left atrial dimensions than did control subjects (3.7 +/- 0.7 vs 4.7 +/- 0.6 cm, p less than 0.001, 2.4 +/- 0.8 vs 2.9 +/- 0.7 cm, p less than 0.02 and 3.2 +/- 0.5 vs 3.8 +/- 0.9 cm, p less than 0.01, respectively). Though the wall thickness of the interventricular septum did not differ between the study groups, the left ventricular posterior walls of the bedridden group were significantly thinner than in the control group (0.8 +/- 0.2 vs 1.0 +/- 0.2 cm, p less than 0.01). The bedridden group had a significantly lower stroke index (26.9 +/- 6.2 vs 47.0 +/- 11.1 ml/m2, p less than 0.001) and cardiac index (1.84 +/- 0.52 vs 3.15 +/- 0.63 l/min/m2, p less than 0.001) than did the control group. Left ventricular mass index and left ventricular systolic stress were significantly lower in bedridden patients than in control subjects (88.0 +/- 18.1 vs 143.5 +/- 30.9 g/m2, p less than 0.001, and 135.9 +/- 4.9 vs 186.6 +/- 35.7 10(3) dynes/cm2, p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fos plays no role in apoptosis of epithelia in the mouse male accessory sex organs and uterus

Roles of Fos in apoptosis of epithelia in the mouse male accessory sex organs and uterus were investigated using Fos-deficient mice. Normal 30- and 50-day-old and Fos-deficient 50-day-old male and female mice were castrated, and testosterone propionate and estradiol-17 beta were daily injected into male and female mice, respectively, for 5 days. An apoptotic index (a percentage of apoptotic cells) in the epithelium was examined from the day following the last injection (day 1) to day 8. The body weights and the weights of the ventral prostate (VP), coagulating gland (C), seminal vesicle (SV) and epididymis (Ep) and uterus of 50-day-castrated Fos-deficient mice on day 1 suggested that the development of these mice corresponded to that of 30-day-castrated normal mice at the most. The extents of apoptosis estimated by an apoptotic index in the VP, C, SV, Ep and uterus in 50-day-castrated Fos-deficient mice were comparable to those in 30-day-castrated normal mice. The extents of apoptosis in the SV, Ep and uterus in 30-day-castrated normal and 50-day-castrated Fos-deficient mice were similar to those in 50-day-castrated normal mice, while the extents of apoptosis in the VP and C in the former two groups of mice were less than those in the latter mice. The present results show that Fos-deficiency does not affect apoptosis in the SV, EP and uterus. However, the extents of apoptosis in the VP and C were less in 50-day-castrated Fos-deficient mice than in 50-day-castrated normal mice. This seems to be due to the retarded development of 50-day-castrated Fos-deficient mice, but not to a role of Fos in apoptosis.