Small Cell Carcinoma of the Prostate: A Case Report

A case of small cell carcinoma of the prostate without a primary lesion in the lung was reported. The cancer was diagnosed after the patient complained of lumbago caused by bone metastasis. The tumor was 5.9 times 5.0 times 4.6cm. The patient was treated with 4 courses of chemotherapy using cisplatin and etoposide. The tumor diminished to 4.0 times 4.0 times 3.5 cm after completion of the 4 courses of treatment. Prostatic antigen levels were less than 1.0ng/mL during the therapy. Neuron-specific enolase levels were 35.9ng/mL at the beginning of therapy, and decreased to 7.4 ng/mL after completion of 4 courses of treatment. The patient died 3 months after the completion of treatment. This regimen had some value for inhibiting the growth of small cell carcinoma.     

Analysis of circulating thyroid-stimulating activities in pregnant women with Graves' disease: differential measurement of activities induced by TSH receptor antibody and hCG]

Thyrotoxicosis in Graves' disease is often aggravated in early pregnancy and this aggravation is associated with postpartum relapse of thyrotoxicosis. To examine whether thyroid-stimulating TSH receptor antibody (TSAb) or human chorionic gonadotropin (hCG), which also has thyroid-stimulating activity (TSA), is responsible for this early aggravation, the respective TSA due to TSAb or hCG were evaluated with a sensitive cAMP accumulation assay using FRTL-5 cells. TSA, which was detectable in all of 11 women in normal early pregnancy, correlated positively with serum hCG level, but was abolished completely by the pretreatment of serum samples with the solid-phase hCG antibody coupled with Sepharose-4B. Total TSA in the model samples of mixture of Graves' and pregnant sera (Gr + Preg), was reduced by the pretreatment with the solid-phase antibody, just corresponding with the reduction in hCG-induced TSA. Total TSA in early pregnant sera in 15 patients with Graves' disease, decreased significantly but was still positive even by the pretreatment with the hCG antibody. Pregnancy-associated changes in TSA was examined serially in a patient with Graves' disease, and hCG-induced TSA increased predominantly along with the serum thyroid hormone in early aggravation period. These data indicate that (1) the respective TSA due to TSAb or hCG can be differentially measured by using the solid-phase hCG antibody and (2) hCG plays an important role for aggravation of Graves' thyrotoxicosis in early pregnancy.     

Exercise BP response in subjects with high-normal BP: exaggerated blood pressure response to exercise and risk of future hypertension in subjects with high-normal blood pressure

OBJECTIVES: This study was designed to assess the clinical usefulness of an exaggerated blood pressure (BP) response to exercise (EBPR) in predicting the development of hypertension from a high-normal state. BACKGROUND: Exaggerated BP response during both dynamic and isometric exercises are associated with increased risk of future hypertension, while the significance of these responses concerning the identification of individuals with high-normal BP who are prone to develop hypertension is unknown. METHODS: The study population comprised a sample of 239 men with high-normal BP (aged 42.3 +/- 5.9 years) who underwent a symptom-limited bicycle ergometer exercise testing at baseline and then were followed for 5.1 years. RESULTS: The Kaplan-Meier survival analysis showed that the subjects in the upper quartile of BP response to exercise had a significantly higher cumulative incidence of hypertension on follow-up than those in the middle two and lower quartiles (log-rank test, p < 0.05). Multivariate analysis using the Cox proportional hazards survival model showed that the EBPR was significantly and independently associated with the risk of developing hypertension after adjustment for some traditional risk factors for hypertension (RR = 2.31, 95% confidence interval = 1.45 to 6.25). CONCLUSIONS: These findings suggest that an EBPR is an important risk factor for new-onset hypertension from a high-normal state and, thus, exercise testing can provide valid information that may help identify individuals with high-normal BP at a greater risk of future hypertension.     

Locomotor training with partial body weight support in patients with Parkinson's disease and stroke: Its efficacy and neural mechanisms

Locomotor training with partial bodyweight support on the treadmill is applicable to neuro-rehabilitation for various gait disorders caused by neurological diseases. Although neural mechanisms for the efficacy remain unclear, recent optical neuroimaging studies using near infra-red spectroscopy have suggested that this training might modify the hierarchical locomotor control system, including several cortical motor areas and the central pattern generator in the spinal cord.     

Enzyme immunoassay of 17-hydroxyprogesterone in dried blood spot on filter paper using specific antibody for 17-hydroxyprogesterone

Specific antiserum for 17-hydroxyprogesterone (17-OH-P) was prepared by immunizing 7 alpha-(2-carboxyethylthio)-17-OH-P conjugated bovine serum albumin (BSA) in rabbits. Using this antiserum, 17-OH-P enzyme immunoassay for dried blood spots on filter paper was established. As a label, alkaline phosphatase was coupled covalently with 7 alpha-carboxy-methylthio-17-OH-P by carbodiimide method. B/F separation was carried out by the addition of anti-rabbit IgG goat antiserum. All specimens used were punched out with a paper puncher of 3mm diameter. The assay sensitivity was 2pg/tube, which was estimated by two standard deviation at zero concentrations of the calibration curve. Cross reactivities of this antibody were as follows: 11-deoxycortisol (8.21%), 17-OH-pregnenolone (3.33%), progesterone (1.67%), 11-deoxycorticosterone (0.31%), cortisol (0.16%), pregnenolone-3-sulfate Na salt (0.03%), dehydroepiandrosterone (DHEA) (less than 0.03%), 16 alpha-OH-DHEA (less than 0.03%), DHEA-3-glucuronide (less than 0.03%), DHEA-3-sulfate Na salt (less than 0.03%), pregnenolone (less than 0.02%). Intra- and inter-assay coefficient of variations were 4-14% and 9-18%, respectively. In normal babies, 17-OH-P concentrations measured directly (without sample extraction) were below 23pg/disk (n=204). The histogram of 17-OH-P level in normal babies obtained by the direct method was distributed lower than that obtained by the enzyme immunoassay system (range: 4-79pg/disk, n=268) which used antibody raised against 17-OH-P-3-O-carboxymethyloxime conjugated BSA (Enzaplate, Sapporo Diagnostic Laboratory).(ABSTRACT TRUNCATED AT 250 WORDS)     

Epitope mapping of human thyrotropin

Epitope mapping of hTSH was carried out using 19 monoclonal antibodies prepared with hTSH or its beta-subunit as antigen. The affinity constants of the monoclonal antibodies ranged from 9.6 X 10(7) to 5.7 X 10(9) mol/l for hTSH. The binding activities of monoclonal antibodies were maintained or in some cases rather enhanced after removal of the sugar moiety of the subunits of hTSH, and completely diminished after reduction of intramolecular S-S bonds in the subunits of hTSH. Ten monoclonal antibodies recognized the epitopes on hTSH (alpha:beta subunit combined form) and on free alpha-subunit form. Eight other antibodies recognized the epitopes on free/or combined form of beta-subunit, all of which did not recognize any other human glycoprotein hormones. The monoclonal antibodies directed against the alpha-subunit could bind also other human glycoprotein hormones to a varying extent. On the basis of results from competitive binding studies, the antibodies directed against alpha-subunit and those against beta-subunit were each classified into five subgroups recognizing different antigenic determinants. The remaining one antibody recognized an epitope expressed only by hTSH and not by the free subunits. In addition, a positive cooperativity on the binding of hTSH was observed between monoclonal antibodies directed towards a particular epitope on the alpha-subunit and those towards a epitope on the beta-subunit. From these data, two-dimensional map of epitopes on hTSH was constructed. The epitopes on each subunit were found to form a cluster with complicated overlapping, suggesting a highly conformational structure.     

Streamlined human antibody generation and optimization by exploiting designed immunoglobulin loci in a B cell line

Monoclonal antibodies (mAbs) are widely utilized as therapeutic drugs for various diseases, such as cancer, autoimmune diseases, and infectious diseases. Using the avian-derived B cell line DT40, we previously developed an antibody display technology, namely, the ADLib system, which rapidly generates antigen-specific mAbs. Here, we report the development of a human version of the ADLib system and showcase the streamlined generation and optimization of functional human mAbs. Tailored libraries were first constructed by replacing endogenous immunoglobulin genes with designed human counterparts. From these libraries, clones producing full-length human IgGs against distinct antigens can be isolated, as exemplified by the selection of antagonistic mAbs. Taking advantage of avian biology, effective affinity maturation was achieved in a straightforward manner by seamless diversification of the parental clones into secondary libraries followed by single-cell sorting, quickly affording mAbs with improved affinities and functionalities. Collectively, we demonstrate that the human ADLib system could serve as an integrative platform with unique diversity for rapid de novo generation and optimization of therapeutic or diagnostic antibody leads. Furthermore, our results suggest that libraries can be constructed by introducing exogenous genes into DT40 cells, indicating that the ADLib system has the potential to be applied for the rapid and effective directed evolution and optimization of proteins in various fields beyond biomedicine.