Prognosis of operable squamous cell carcinoma of the esophagus. Relationship with clinicopathologic features and DNA ploidy

Fluorescence in situ hybridization (FISH) was performed on human interphase sperm nuclei to determine the utility of this technique for aneuploidy detection. Repetitive DNA sequences specific for chromosomes 1, 12 and X were biotinylated and hybridized with mature sperm, which had been treated with cetyltrimethylammonium bromide and dithiothreitol to render them accessible to the probes. Detection of bound probe was accomplished with fluoresceinated avidin and antiavidin. For each of the chromosomes studied, chromosome number was determined by counting the fluorescent signals, representing hybridized regions, within the sperm nuclei. The frequencies for disomy, that is for nuclei containing two signals, for chromosomes 1, 12 and X were 0.06%, 0.04% and 0.03%, respectively. The congruence of these results with those determined by the cross-species hamster oocyte-human sperm assay, and the high efficiency of hybridization indicate that FISH is a sensitive and reliable tool for aneuploidy detection in human sperm.     

Pharmaceutical services in the treatment of hemophiliac patients

Pharmaceutical services in the treatment of hemophiliac patients in Sweden are described. To prevent arthropathy and improve quality of life, patients with severe hemophilia receive prophylactic treatment. Hemophiliac patients are referred for diagnosis, treatment, and follow-up to one of three hemophilia treatment centers. Patients are seen once or twice yearly for routine checkups. A new system for the distribution of antihemophilic factor and factor IX has been implemented to improve availability and reduce risks and costs. Patients registered at a center receive antihemophilic factor or factor IX from the corresponding hospital pharmacy. The number of different manufactured batches to which a patient can be exposed is restricted, and complete distribution data are recorded for each patient, enabling follow-up studies and facilitating withdrawals of faulty batches. Distribution of emergency kits to patients who do not receive supervised home therapy ensures the availability of treatment for bleeding episodes. Two studies performed to explore ways to reduce drug waste led to improvements in patient information, product guidelines, and equipment and a better understanding of the problems associated with product changes. Specialized pharmaceutical services in Sweden contributed to successful hemophilia treatment and reduced its cost.     

Anorexia

The segregation products in zygotes of females heterozygous for the mouse Rb(6.16) translocation were studied. Of 191 first-cleavage metaphase zygotes recovered from 16 females mated to chromosomally normal males, 132 were cytogenetically analyzed after sequential G- and C-banding. There were no products of adjacent segregation, since the six chromosomal imbalances were unrelated to the translocation. Alternate segregation was seen in 126 (95.5%) of the zygotes, with 85 being chromosomally normal and 41 carrying the translocation. These results indicate preferential alternate segregation and a significant deviation from the Mendelian 1:1 ratio (P < 0.005) for reciprocal alternate segregants, as seen earlier for males with this translocation. However, the approximately 2:1 ratio for normal-to-balanced segregants in females is lower than the ratios consistently seen for males. This supports the notion that there are different underlying causes of the distortion in the sexes.     

Comparative image cytometric DNA ploidy of liver cell dysplasia and hepatocellular carcinoma

Large-cell liver cell dysplasia (LCD), suggested to be a preneoplastic change that progresses to hepatocellular carcinoma (HCC), has a reported frequency of DNA aneuploidy by flow cytometry intermediate between that of nonneoplastic liver (0%) and HCC (80%). We assessed DNA ploidy by image cytometry of Feulgen-stained 5-microns sections of 30 livers with LCD and of 60 HCCs (29 with LCD in adjacent nonmalignant liver). All 30 LCDs were aneuploid, 27 (90%) of which were multiploid--11 (41%) with hyperdiploid and hypertetraploid peaks. Forty-eight (80%) HCCs were aneuploid; in nine of 20 (42%) with a hyperdiploid peak, a hyperdiploid peak was also present in the LCDs, but in none was there less than 0.24 between DNA indices. Besides the 12 (20%) diploid HCCs, a diploid peak was present in four heterogenous, three multiploid, and six HCCs with two phenotypes and two genotypes, one of which was diploid. One aneuploid/hyperdiploid peak in each of 22 nonneoplastic and 24 cirrhotic livers did not have a corresponding LCD or HCC aneuploid peak. These data do not suggest that dysplastic hepatocytes form a single mutant clone that progresses to HCC.     

Adenosine A2A receptors modulate the binding characteristics of dopamine D2 receptors in stably cotransfected fibroblast cells

In membrane preparations from rat striatum, where adenosine A2A and dopamine D2 receptors are coexpressed, stimulation of adenosine A2A receptors was found to decrease the affinity of dopamine D2 receptors for dopamine agonists. We now demonstrate the existence of this antagonistic interaction in a fibroblast cell line (Ltk-) stably transfected with the human dopamine D2 (long-form) receptor and the dog adenosine A2A receptor cDNAs (A2A-D2 cells). In A2A-D2 cells, but not in control cells only containing dopamine D2 receptors (D2 cells), the selective adenosine A2A agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethyl-carboxamido adenosine (CGS 21680) induced a 2-3-fold decrease in the affinity of dopamine D2 receptors for dopamine, as shown in competition experiments with dopamine versus the selective dopamine D2 antagonist [3H]raclopride. By contrast, activation of the constitutively expressed adenosine A2B receptors with 5'-N-ethyl-carboxamidoadenosine (NECA) did not modify dopamine D2 receptor binding. In A2A-D2 cells CGS 21680 failed to induce or induced only a small increase in adenosine-3',5'-cyclic-monophosphate (cAMP) accumulation. In D2 cells NECA- or forskolin-induced adenylyl cyclase activation was not associated with any change in dopamine D2 receptor binding. These results indicate that adenylyl cyclase activation is not involved in the adenosine A2A receptor-mediated modulation of the binding characteristics of the dopamine D2 (long-form) receptor.     

The effect of kind of carbohydrate in the diet and use of oral contraceptives on metabolism of young women. II. Serum lipid levels

The response of lipids in the blood between two groups of six young women was compared. Group 1 took oral contraceptives and group 2 had never taken oral contraceptives. Two experimental diets supplied about 13% of the calories from protein, 36% from fat, and 51% from carbohydrate. Of the carbohydrate, 84% was either sucrose or wheat starch. Each diet was fed for 4 weeks in a cross-over design. In the portion of the research presented here, subjects were fed a high sucrose meal before each dietary period and after weeks 1 and 3 of each dietary period. Blood lipids were measured before and 30, 60, 120, and 180 min after each meal. Cholesterol and lipoproteins were not affected by the sucrose meal, but free fatty acid levels decreased significantly in both groups. The serum levels of triglycerides, beta-lipoproteins, and cholesterol were significantly higher in users than in nonusers of oral contraceptives. Free fatty acid levels were affected by an interaction between diet and time, and the decrease in response was greater after the sucrose than after the wheat starch diet. Triglycerides, cholesterol, and total lipids were not significantly different after the two carbohydrate diets.     

A hydrogen-powered mass transit system

Hydrogen's application to mass transit systems is considered. A 21-passenger bus is converted to hydrogen using a Dodge engine which has been modified for high compression operation. Backfiring and nitric oxide pollution formation are controlled by a water injection technique. Hydrogen fuel storage for the experimental prototype is accomplished by two metal hydride containers using an iron-titanium alloy. Data are presented regarding equipment conversion and design, energy resource utilization, economics, and safety.     

A population-based exposure model for benzene

A model of daily-average inhalation exposures and total-absorbed doses of benzene to members of large populations was developed as part of a series of multimedia exposure and absorbed dose models. The benzene exposure and dose model is based upon probabilistic rather than sequential simulation of time-activity patterns, a simpler approach to modeling personal benzene exposures than other existing models. An important innovation of the benzene model is the incorporation of an anthropometric module for generating correlated exposure factors used to estimate absorbed doses occurring from inhalation, ingestion, and dermal absorption of benzene. A preliminary validation exercise indicates that the benzene model produces reasonable estimates of the distribution of benzene personal air concentrations expected for a large population. Uncertainty about specific percentiles of the predicted distributions of personal air concentrations was found to be dominated by uncertainty about microenvironmental benzene concentrations rather than time-activity patterns, and uncertainty about total absorbed doses was dominated by a lack of knowledge about the true absorption coefficient for benzene in the lung rather than knowledge gaps about microenvironmental concentrations or intake rates. The results of this modeling effort have implications for environmental control decisions, including evaluation of source control options, characterization of population and individual risk, and allocation of resources for future studies.