Development of male contraceptive vaccine--a perspective

Anti-disialoganglioside (GD2) monoclonal antibodies (MAbs) have been used in vivo for immunolocalization and in phase I and II trials to target disseminated neuroblastoma, the most common extracranial solid tumor in children. However, the efficacy of these first-generation MAbs is likely to be improved by using engineered anti-GD2 antibodies. The generation of single-chain antibody fragments (scFv) could be very helpful as these molecules can be further modified to produce recombinant molecules with pre-defined properties such as immunotoxins, chimeric, or bispecific antibodies. Thus, a scFv directed against GD2 (scFv 7A4) was cloned, sequenced, and expressed. Its binding properties were characterized and compared to that of the parental MAb 7A4. Nucleotide sequence analysis of the scFv 7A4 indicated that its VH region belongs to the V region IIID subgroup and the V kappa to the V region II subgroup. The scFv 7A4 bound to GD2+ neuroblastoma cell lines but not to GD2- cell lines or to GD2- cells isolated from peripheral blood. ELISA and thin-layer chromatography (TLC) indicated that it retained the anti-GD2 specificity, and exhibited a slight cross-reaction with GD3 as the parental MAb. This scFv makes it possible to develop new useful reagents through genetic engineering for adjuvant tumor therapy.     

p53 and K-ras status in duodenal adenomas in familial adenomatous polyposis

BACKGROUND: The genetic alterations in patients with familial adenomatous polyposis (FAP) and duodenal adenomas are poorly characterized when compared with data relating to colorectal tumorigenesis in the same patients. METHODS: Point mutation of the K-ras oncogene and point mutation and overexpression of the TP53 tumour suppressor gene were investigated in 32 duodenal polyps (seven without mucosal pathology, 23 with mildly dysplastic adenomas and two with moderately dysplastic adenomas) from 21 patients with FAP. RESULTS: K-ras mutation, TP53 mutation or positive p53 staining were not found in duodenal polyps without histological abnormality. Of 25 duodenal adenomas, K-ras mutation was found in three (two mildly dysplastic, one moderately dysplastic), 20 showed positive p53 immunostaining, and mutation of the TP53 gene was found in one moderately dysplastic adenoma. p53 protein overexpression in duodenal adenomas was significantly more frequent than mutation of either K-ras or TP53 (P < 0.01). CONCLUSION: p53 dysfunction is a hallmark of duodenal adenomas in patients with FAP. Overexpression may indicate DNA damage and thus an early step in tumorigenesis.     

Lack of effect of food on the steady state pharmacokinetics of BMS-181101, an antidepressant, in healthy subjects

An annual atmospheric pollen survey was performed for 14 consecutive years in the autumn at Sakado city, Saitama prefecture. The survey was performed on the transition of pollen dispersion of major allergen plants: ragweed (Ambrosia spp.), Humulus japonicus, Artemisia spp. and Gramineae. 1. Annual total pollen count of ragweed showed marked increases beginning from 1991. Total pollen count in 1991 was 8.8 times and that in 1996 was 18.6 times that in 1983. This increase is probably caused by marked proliferation of giant ragweed which is left without mowing as it is on a dry riverbed, and consequently produces much more pollen than short ragweed. 2. Annual increases in total pollen counts of other major plants which disperse their pollen in the same season as ragweed were 0.95 times in 1991 and 0.5 times in 1996 that in 1983 for Humulus japonicus, 0.68 times in 1991 and 1.5 times in 1996 that in 1983 for Artemisia spp. and 1.3 times in 1991 and 1.4 times in 1996 that in 1983 for Gramineae. None of these species showed a marked increase of pollen dispersion although they showed some annual variation. The above findings suggest that changes in the proliferous state of various allergenic plants due to environmental change should be considered with respect to characteristics of pollen allergy.     

Changes of telomere length cause reciprocal changes in the lifespan of mother cells in Saccharomyces cerevisiae

Budding yeast cells divide asymmetrically, giving rise to a mother and its daughter. Mother cells have a limited division potential, called their lifespan, which ends in proliferation-arrest and lysis. In this report we mutate telomerase in Saccharomyces cerevisiae to shorten telomeres and show that, rather than shortening lifespan, this leads to a significant extension in lifespan. This extension requires the product of the SIR3 gene, an essential component of the silencing machinery which binds to telomeres. In contrast, longer telomeres in a genotypically wild-type strain lead to a decrease in lifespan. These findings suggest that the length of telomeres dictates the lifespan by regulating the amount of the silencing machinery available to nontelomeric locations in the yeast genome.     

Long-term outcome in acute myocardial infarction patients admitted to hospitals with and without on-site cardiac catheterization facilities. MITI Investigators. Myocardial Infarction Triage and Intervention

BACKGROUND: Previous studies have documented the strong association between availability of on-site cardiac catheterization facilities and increased use of coronary angiography in patients with acute myocardial infarction (AMI). Although these studies have shown little influence of the availability of catheterization labs on hospital mortality, no long-term follow-up has been reported. METHODS AND RESULTS: From a cohort of 12,331 AMI patients admitted to 19 Seattle area hospitals, we compared long-term outcome in 7985 patients admitted to hospitals with and 4346 patients admitted to hospitals without on-site catheterization labs. During the index hospitalization, patients admitted to hospitals with on-site catheterization were more likely to undergo coronary angiography (67.1% versus 39.3%, P<.0001), coronary angioplasty (32.5% versus 13.2%, P<.0001), or coronary bypass surgery (12.5% versus 9.5%, P<.0001). At 3-year follow-up, patients admitted to hospitals with on-site catheterization labs were more likely to undergo postdischarge angiography (19.2% versus 15.2%, P=.0001) and coronary angioplasty (11.6% versus 8.2%, P<.0001). This was associated with approximately $2500.00 per patient in higher cumulative costs. Despite this higher rate of procedure use, there was no association between admission to a hospital with on-site catheterization facilities and lower long-term mortality (multivariate hazard ratio, 1.0; 95% CI, 0.93 to 1.1., the hazard being associated with admission to hospitals with on-site catheterization facilities). CONCLUSIONS: In an urban area with unconstrained patient transfer mechanisms and high overall cardiac procedure use rates, AMI patients admitted to hospitals without on-site catheterization facilities were managed with fewer procedures during hospitalization and follow-up. This more conservative treatment approach was not associated with any observed increase in long-term mortality.     

Psychological predictors of pain during dental hygiene treatment

This study examined the role of catastrophizing (i.e. a tendency to exaggerate the threat value of potentially painful situations) in predicting pain experience during dental hygiene treatment. Participants in the research were 100 patients undergoing scaling and/or root planing procedures at Dalhousie University's Dental Clinic. Following treatment, participants completed the Pain Catastrophizing Scale, a measure of emotional distress, a pain scale, and the Dental Anxiety Scale-Revised. Participants who scored above the median on the Pain Catastrophizing Scale were classified as catastrophizers, participants who scored below the median were classified as noncatastrophizers. Results showed that catastrophizers reported significantly more dental anxiety, emotional distress and pain than noncatastrophizers; and that distress reactions were more pronounced in men that in women. Discussion focuses on the importance of addressing psychological factors in dental hygiene practice, particularly as they relate to reactions to dental hygiene procedures, and avoidance of dental care.