Serotonin 5- HT (2C) receptor knockout mice: autoradiographic analysis of multiple serotonin receptors.

Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT(2C) receptor knockout mice. The radioligands employed were [(3)H]citalopram, [(3)H]WAY100,635, [(3)H]8-OH-DPAT, [(3)H]GR125743, [(3)H]sumatriptan, [(3)H]MDL100,907, [(125)I](+/-)DOI, [(3)H]mesulergine, [(3)H]5-HT, [(3)H]GR113808, and [(3)H]5-CT. As expected, radioligands that label 5-HT(2C) receptors showed a complete absence of labeling in mutant mice choroid plexus and significantly reduced densities in other brain regions expressing 5-HT(2C) receptors. With the rest of the radioligands, no significant alterations in the densities of labeled sites were found in any brain region. In situ hybridization showed no changes in 5-HT(2A) receptor and serotonin transporter mRNA levels, whereas 5-HT(2C) receptor mRNA levels were reduced in certain brain regions. The present results indicate that the mouse serotonergic system does not exhibit compensatory up- or down-regulation of the majority of its components (serotonin transporter and most 5-HT receptor subtypes) in response to the absence of 5-HT(2C) receptors.     

Eligible Veterans'' Choice Between VA-covered and Non-VA-covered Dental Care

Veterans who were eligible for dental care in Department of Veterans Affairs (VA) facilities at no monetary cost responded to a mailed questionnaire. Seventy-one percent were aware that they were actually eligible for VA dental care. However, only 48 percent reported the VA as their only or primary source of dental care. Eligibility status, perceived quality of VA dental care, use of VA medical care, perception that one's income meets expenses, and perceived need for dental care were significant correlates of using the VA as one's current source of dental care. Level of formal education, perception that one's income meets expenses, transportation pattern, geographic distance from a VA facility, and eligibility status were significant correlates of using the VA as one's current medical care source. Research on VA utilization offers the opportunity to study issues of access to, and use of, a large public health care system whose patients largely receive care at no monetary cost. Veterans' use of VA dental and medical care is apparently influenced by a wide variety of factors, ranging from barriers to access to non-VA systems, to characteristics of the VA delivery system itself, to need for treatment.     

Atributable risk of breast,prostate, and lung cancer in Hawaii due to saturated fat

The dietary data from case-control studies of breast, prostate, and lung cancer in Hawaii revealed that saturated fat was a risk factor for these malignancies. The dietary intakes from the three studies were used to calculate the attributable risk (AR) due to saturated fat. For all ethnic groups combined, the ARs for the highest quartiles of intake were 14.9 percent for female breast cancer, 13.0 percent for prostate cancer, and 23.1 percent for male lung cancer. Our results suggested that a reduction of saturated fat to the lowest quartiles of intake could result in a 10 to 20 percent decrease in risk for these three cancers in Hawaii. We also examined the ethnic-specific risks associated with saturated fat consumption among the Japanese and the Caucasians in the three studies. The ARs for the highest quartiles of intake were notably higher among the Caucasians than the Japanese, primarily due to the difference in their dietary patterns. Although the calculated AR due to saturated fat was higher among the Caucasians than among the Japanese, all persons in the population would derive considerable benefit by reducing their intake of this nutrient.Authors are with the Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, 1236 Lauhala Street, Honolulu, HI 96813, USA. Address correspondence to Dr Hankin. This study was supported in part by NIH Grant PO1 CA 33619.     

Acquired Loss of Red-Cell Wj Antigen in a Patient with Hodgkin''s Disease

A patient with Hodgkin's disease became temporarily Wj-negative with alloanti-Wj in his serum. Four human autoantibodies, and 1 of 2 murine monoclonal antibodies, with serological characteristics of anti-Wj were nonreactive with his red cells, confirming that they have anti-Wj specificity. Six siblings of the patient are all Wj-positive. The patient was also temporarily Anton-negative, and cross-testing between Wj and Anton red cells and antisera showed mutual compatibility, indicating that the antigens are the same. The patient and 3 of his 6 siblings are also of the rare Lu: - 13 phenotype, providing the first evidence that this is an inherited characteristic.     

Anti-tumor immunotherapy via antigen delivery from a live attenuated genetically engineered Pseudomonas aeruginosa type III secretion system-based vector.

Immunotherapy requiring an efficient T lymphocyte response is initiated by antigen delivery to antigen-presenting cells. Several studies have assessed the efficiency of various antigen loading procedures, including microbial vectors. Here a live strain of Pseudomonas aeruginosa was engineered to translocate a recombinant antigenic protein into mammalian cells via the type III secretion system, a bacterial device translocating effector proteins into host cells. Optimization of the vector included virulence attenuation and determination of the N-terminal sequence allowing translocation of fused antigens into cells. In vitro delivery of an ovalbumin fragment by the bacterial vector into dendritic cells induced the activation of ovalbumin-specific CD8(+) T lymphocytes. Mice injected with the ovalbumin-delivering vector developed ovalbumin-specific CD8(+) T lymphocytes and were resistant to a subsequent challenge with an ovalbumin-expressing melanoma. Moreover, in a curative assay, injection of the vaccine vector 5 and 12 days after tumor implantation led to a complete cure in five of six animals. These results highlight the utility of type III secretion system-based vectors for anti-tumor immunotherapy.