Subcellular concentrations of estrone, estradiol, androstenedione and 17 beta-hydroxysteroid dehydrogenase (17-beta-OH-SDH) activity in malignant and non-malignant human breast tissues

Total and subcellular (cytosol and nuclear) concentrations of estrone (E1), estradiol (E2), and androstenedione were determined in non-malignant (n = 61) and malignant (n = 65) human breast tissues obtained from post-menopausal women. The 17 beta-hydroxysteroid dehydrogenase (17 beta-OH-SDH) activity was determined in 800g supernatant fraction. Total estrogens, E1 and E2 levels and 17 beta-OH-SDH activity were significantly (p less than 0.005, 0.0005, 0.001, respectively) higher in malignant than in non-malignant breast tissues. We failed to observe significant changes in subcellular steroid concentrations or enzyme activity associated with patients' obesity or tumor estrogen receptor status. When the steroid levels were analyzed in relation to clinical staging of the disease, nuclear contents of estradiol were significantly higher (p less than 0.005) in Stage-IV patients than in those with less advanced disease (Stages I to III). 17 beta-OH-SDH activity was significantly (p less than 0.001) lower in patients with advanced disease than in those with relatively less advanced (Stages I to III) disease and was positively correlated with tissue concentration of androstenedione. Our present data indicate that differential intracellular metabolism of steroid hormones may have some influence on availability of estradiol at nuclear sites. In postmenopausal women, local interconversion of estrogens may provide sufficient estrogenic stimulus to enhance the growth and progression of breast tumors.     

Comparative effects of pilocarpine in different vehicles on pupil diameter in albino rabbits and squirrel monkeys

Several commercial pilocarpine preparations have been compared for their efficacy of drug delivery as evaluated by changes in pupil diameter, and return to base-line pupil size, in rabbits and squirrel monkeys. Adsorbocarpine, Isoptocarpine, Pilocar, all at 2%, and Pilopine HS gel, 4%, were used. In albino rabbits the order of efficacy, as judged by area under the curve, or maximal pupil diameter change, was Pilopine greater than Isoptocarpine = Adsorbocarpine greater than Pilocar = saline (prepared in this laboratory). In general, greater areas under the curve were associated with greater changes in pupil diameter. Pupil diameter had returned to normal by a maximum of 5 hours after drop instillation. In squirrel monkeys, the maximum pupillary change was statistically (P greater than 0.05) the same for all preparations, as was the percentage change in pupil diameter at 6 hours since pupils were still somewhat constricted at this time after drop instillation. The differences in area under the curve were minor. The greater response in primates compared to rabbits may be due to differences in pigment, intraocular kinetics and a far more active ciliary muscle in primates. Also studied were newly developed, non-surfactant containing, preservative-free polymer- and microparticle-based vehicles. Some of the vehicles, based on cyanoacrylate, modified hyaluronate, anionic copolymers, polyvinyl-pyrrolidone, cross-linked gelatin and microparticles showed greater pupillary changes and areas under the curve in rabbits compared to saline vehicle. When compared to commercial preparations in the monkey eye cyanoacrylate block copolymer and modified hyaluronate showed an increase in efficacy. Polyvinylpyrrolidone, anionic copolymer and cross-linked gelatin were equal to the commercial preparations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the Ca 1 monoclonal antibody in distinguishing oral squamous cell carcinoma from non-malignant or premalignant oral lesions

The Ca antigen has been reported to be present on the surface of malignant but not, with few exceptions, non-malignant cells. We investigated the potential usefulness of the monoclonal Ca 1 antibody in differentiating oral squamous cell carcinoma from non-malignant or premalignant oral neoplasms. Paraffin-embedded sections from 33 biopsy specimens of 12 hyperplastic and 21 neoplastic oral lesions were examined by immunohistochemical staining. Seven of the 33 specimens showed positive staining for Ca antigen. Fifteen of 21 specimens of oral squamous cell carcinoma were negative for Ca antigen, and one case of focal keratosis was positive. The results indicate that the use of the Ca 1 antibody to distinguish oral squamous cell carcinoma from non-malignant or premalignant oral lesions is highly unreliable.     

Wisconsin Card Sorting Test performance in schizophrenia: remediation of a stubborn deficit.

OBJECTIVE: Schizophrenic patients typically perform poorly on the Wisconsin Card Sorting Test, which is a putative index of prefrontal functioning. The authors attempted to remediate the deficits of schizophrenic patients on this measure by giving detailed instructions and monetary reinforcement. METHOD: Forty-six inpatients with chronic schizophrenia and 20 control subjects with other psychiatric illnesses were given the Wisconsin Card Sorting Test under four conditions that varied in monetary reinforcement and level of instructions. The schizophrenic patients were given the Brief Psychiatric Rating Scale (BPRS) and three information processing measures (the Continuous Performance Test, Span of Apprehension, and Pin Test). RESULTS: Schizophrenic patients performed worse than psychiatric control subjects across most conditions. Monetary reinforcement had little effect on performance, but detailed instructions significantly improved the scores for both groups. When instructions were withdrawn and monetary reinforcement was maintained, both groups continued to show improved performance over baseline. Symptoms were not significantly associated with Wisconsin Card Sorting Test performance. One measure (the Pin Test) correlated significantly with performance on the Wisconsin Card Sorting Test. CONCLUSIONS: The results suggest the importance of combining motivational with instructional factors for training psychiatric patients in problem solving.     

Morphogen gradients, positional information, and Xenopus: interplay of theory and experiment.

The idea of morphogen gradients has long been an important one in developmental biology. Studies with amphibians and with Xenopus in particular have made significant contributions to demonstrating the existence, identity, and mechanisms of action of morphogens. Mesoderm induction and patterning by activin, nodals, bone morphogenetic proteins, and fibroblast growth factors have been analyzed thoroughly and reveal recurrent and combinatorial roles for these protein growth factor morphogens and their antagonists. The dynamics of nodal-type signaling and the intersection of VegT and beta-catenin intracellular gradients reveal detailed steps in early long-range patterning. Interpretation of gradients requires sophisticated mechanisms for sharpening thresholds, and the activin-Xbra-Gsc system provides an example of this. The understanding of growth factor signal transduction has elucidated growth factor morphogen action and provided tools for dissecting their direct long-range action and distribution. The physical mechanisms of morphogen gradient establishment are the focus of new interest at both the experimental and theoretical level. General themes and emerging trends in morphogen gradient studies are discussed.     

Bionomics of Anopheles maculatus complex and their role in malaria transmission in Thailand

The bionomics of Anopheles maculatus complex and its role in malaria transmission were conducted in Pakchong and Sadao districts, Nakhon Ratchasima and Songkhla provinces, respectively, from January 1984 to July 1985. In Pakchong, An. maculatus species A was the most dominant species, followed by species B form F and species C which was rare. The densities of species A and species B form F were high between July and November, with their peaks in October. Biting activities of both species occurred through out the night, with a major peak during the first quarter of the night on all seasons. In Sadao, only An. maculatus species B form E was detected with peak densities between February and June. Biting activities of this species varied according to seasons. The prevalence of mosquitoes was influenced by monthly rainfall, relative humidity and air-temperature. All species of female An. maculatus complex studied prefered to feed on animal rather than on human, and tended to bit human more outdoors than indoors, and thus exhibiting a zoophilic and exophagic behaviour. Life expectancies of An. maculatus species A ranged from 1.6 to 6.6 days, species B form F from 1.1 to 8.1 days, and species B form E from 0.7 to 21.2 days. The natural malaria infection rate was very low. Out of 4,430 guts dissected, only 0.23% were found infected with oocysts. There were no sporozoites detected in the 4,472 dissected salivary glands.