Covalent binding of 7,12-dimethylbenz[a]anthracene to lymphoid and nonlymphoid tissues following oral administration to B6C3F1 mice.

Previous studies have shown that 7,12-dimethylbenz[a]anthracene (DMBA) is cytotoxic to various murine lymphoid tissues, including the spleen, thymus, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs). In the present studies, we measured the amount of covalent binding of [3H]DMBA to lymphoid and nonlymphoid tissues and correlated these findings with the overall levels of [3H]DMBA (and derived substances) present in various tissues following a single oral administration to mice. Results show that [3H]DMBA was taken up relatively rapidly from the GI tract and that it was nearly completely eliminated within 24 hr via the feces. Peak plasma levels were obtained approximately 6 hr after gavage, and most organs (including brain, heart, liver, lung, kidney, spleen, and thymus) achieved their peak level of DMBA at this time. Maximal concentrations of DMBA were detected in gut-associated lymphoid tissues (i.e., PPs and MLNs) at 4 hr, during which time covalent binding of [3H]DMBA was also maximal. The time course for covalent binding was different in the liver, lung, thymus, and spleen, peaking at 6-12 hr. The amount of covalent binding of [3H]DMBA and derived metabolites in the spleen was more than twice that seen in the other tissues examined. Since the spleen has previously been found to be less sensitive to DNA fragmentation induced by DMBA than the PPs, these results suggest that covalent binding may not be the primary determinant of lymphotoxicity in these organs.     

The Membrane Lipid Cholesterol Modulates Anesthetic Actions on a Human Brain Ion Channel

Background: Molecular theories of general anesthesia often are divided into two categories: (l) Anesthetics may bind specifically to proteins, such as ionic channels, and alter their function directly, and (2) anesthetics may alter the functions of integral membrane proteins indirectly through modification of the physical properties of the membrane. Recent studies have provided evidence that anesthetics can bind to proteins and modify their function directly, bringing into question the role of the membrane in anesthetic interactions. To reexamine the role of membrane lipids in anesthetic interactions, an experimental approach was used in which the membrane lipid composition could be systematically altered and the impact on anesthetic interactions with potential targets examined.

Methods: Sodium channels from human brain cortex were incorporated into planar lipid bilayers with increasing cholesterol content. The anesthetic suppression of these channels by pentobarbital was quantitatively examined by single channel measurements under voltage-clamp conditions.

Results: Changes in cholesterol content had no effect on measured channel properties in the absence of anesthetic. In the presence of pentobarbital, however, cholesterol inhibited anesthetic suppression of channel ionic currents, with 1.9% (weight/weight, corresponding to 3.5 mol%) cholesterol decreasing anesthetic suppression of sodium channels by half.     

Yersinia enterocolitica causing suppurative arthritis of the shoulder.

Yersinia enterocolitica is a rare cause of extra-intestinal disease. A case in a 60 year old butcher with hepatic cirrhosis who developed suppurative arthritis of the shoulder caused by Y enterocolitica is presented. There was no evidence of gastrointestinal infection or septicaemia. The severity of the illness was associated with various factors, including the underlying disease, the type of occupation, and the difficulties encountered in defining the optimal therapeutic regimen.     

CDC's consensus set of health status indicators: monitoring and prioritization by state health departments.

A survey assessed the extent to which state health departments monitor and prioritize the Centers for Disease Control and Prevention's consensus set of health status indicators. A response rate of 100% was obtained. Although mortality indicators are often monitored, only 75.5% of the states monitor work-related injury deaths. Most states monitor the incidence of acquired immunodeficiency syndrome, measles, tuberculosis, and syphilis. Low birthweight, births to adolescents, and lack of prenatal care are monitored in nearly all states and are considered high-priority problems. Only 46.9% of states are monitoring poor air quality, and only 58.8% are monitoring childhood poverty. Survey results suggest a need for standardized assessment of indicators for policy development and program planning.     

Overexpression of parathyroid hormone-related protein in the skin of transgenic mice interferes with hair follicle development.

Parathyroid hormone-related peptide (PTHrP) was initially discovered as the cause of the syndrome of humoral hypercalcemia of malignancy. Subsequently, the PTHrP gene has been shown to be expressed in a wide variety of normal tissues, including skin. Because the biological function of PTHrP in skin remains unknown, we used the human keratin 14 promoter to target overexpression of PTHrP to the skin of transgenic mice. We achieved a 10-fold level of overexpression in skin, and human keratin 14 promoter-PTHrP transgenic mice displayed a disturbance in normal hair follicle development. These mice either failed to initiate follicle development or showed a delay in the initiation of follicles. These findings suggest that PTHrP normally plays a role in the early stages of hair follicle development and support previous speculation that the peptide may function in regulating cellular differentiation.     

Effect of a patellar realignment brace on patellofemoral relationships: Evaluation with kinematic MR imaging

The effect of a newly developed patellar realignment brace was evaluated in 21 patellofemoral joints (19 patients) with patellar subluxation (13 joints with lateral subluxation and eight with medial subluxation) by using active-movement, loaded kinematic magnetic resonance (MR) imaging. Sixteen patellofemoral joints (76%) demonstrated a qualitative correction of or improvement in patellar subluxation (ie, centralization of the patella or a decrease in the displacement of the patella) after application of the brace. Four of the five “failures” occurred in patellofemoral joints that had patella alta and/or dysplastic bone anatomy. These results indicate that the patellar realignment brace was able to counteract patellar subluxation in the majority of patellofemoral joints studied, as shown by active-movement, loaded kinematic MR imaging. This brace appears to be useful for conservative treatment of patients with patellofemoral joint pain secondary to patellar malalignment and maltracking.     

Cloning of a cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase from rat liver and its regulation by thyroid hormones.

A full-length 2.4-kb cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) was cloned from rat liver using PCR techniques. The cloned gene encodes a protein of 727 amino acids. The calculated molecular mass of 80,898 Da is higher than the apparent molecular mass observed by SDS/PAGE (74,000 Da) of the purified enzyme. This result indicates that the enzyme is synthesized as a precursor with a putative mitochondrial signal sequence. mRNA for this gene was detected in liver, heart, muscle, brain, testes, and pancreas. With the exception of testes, basal expression levels were very low in all tissues examined. However, application of thyroid hormones led to a 10- to 15-fold increase in liver glycerol-3-phosphate dehydrogenase mRNA, whereas hypothyroidism further decreased the mRNA level.     

Bombesin improves survival from methotrexate-induced enterocolitis.

OBJECTIVE: The authors determined whether bombesin could improve survival from methotrexate (MTX)-induced enterocolitis. SUMMARY BACKGROUND DATA: Bombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. METHODS: On treatment day 0, 60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 micrograms/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. RESULTS: Bombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). CONCLUSION: Bombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents.     

High-resolution loading tests in the study of genetic heterogeneity in gangliosidosis fibroblasts

Summary GM₁- and GM₂-gangliosides were isolated from brain and radio-labelled. The labelled moieties were localized by hydrolysis with lysosomal enzymes, followed by thin-layer chromatography of the products. High-resolution loading tests with labelled gangliosides were developed and found to differentiate infantile and juvenile forms of GM₁- and GM₂-gangliosidoses as well as the identification of B, O and AB types of GM₂-gangliosidosis.