Mesothelin, a differentiation antigen, is a 40-kD glycosylphosphatidylinositol-linked cell-surface glycoprotein, that is present on the surface of normal mesothelium and is overexpressed in many patients with epithelial ovarian cancer and malignant mesotheliomas. Monoclonal antibody K1 is a murine immunoglobulin G1 that recognizes mesothelin. LysPE38QQR is a truncated form of Pseudomonas exotoxin that lacks the cell-binding domain, but retains the translocation and adenosine diphosphate-ribosylation domains. It has a single lysine residue near the amino terminus that is available for conjugation to antibodies. To prevent chemical conjugation of the antibody to lysine residues at the C-terminus of Pseudomonas exotoxin, the two lysine residues at positions 590 and 606 were mutated to glutamine, and the lysine residue at position 613 was mutated to arginine. Monoclonal antibody K1 was chemically conjugated with LysPE38QQR, by modifying the antibody with sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate and coupling it with SPDP N-succinimidyl 3-(2-pyridyldithio)propionate-modified LysPE38QQR. The resulting immunotoxin K1-LysPE38QQR was highly toxic to A431-K5 cells (a human epidermoid carcinoma cell line transfected with a mesothelin expression plasmid) with a half-maximal inhibitory concentration of 3-6 ng/mL. The immunotoxin had negligible activity against A431 cells, which do not express mesothelin (median inhibitory concentration > 100 ng/mL). This immunotoxin also caused complete regression of tumors in nude mice that received xenografts of mesothelin-positive human carcinomas. These results show that immunotoxins directed against mesothelin are a therapeutic option that merits further investigation for the treatment of ovarian cancer and malignant mesotheliomas.

ADP Ribose Transferases↗

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Effect of thiamine on glucose utilization in hepatic cirrhosis.

Thiamine, an essential co-enzyme, improves glucose utilization. Thiamine hydrochloride (50 mg per capita per day for 30 days), given to 25 patients with liver cirrhosis who had hyperglycaemia, produced a significant reduction (P less than 0.001) in blood glucose levels. It is therefore suggested that thiamine supplements be given to cirrhotics with hyperglycaemia, to improve glucose utilization.

Adult↗

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Late-life-onset panic disorder: clinical and demographic characteristics of a patient sample.

Although panic disorder is generally believed to begin in young adulthood, 13 cases of panic disorder with an initial onset after age 60 years have recently been seen at our clinics. Other than the time of life in which the first panic attack occurred, clinical and demographic profiles of these 13 patients were similar to those that have been reported for panic disorder patients whose panic began earlier in life. These findings indicate that panic disorder can affect older adults with no previous history of panic attacks, but further research is needed to determine the clinical and theoretical significance of late-life-onset panic disorder.

Age of Onset↗

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Cerebrospinal fluid otorrhea after head injury (case report).

Explore the source record for details and available documents.

Cerebrospinal Fluid Otorrhea↗

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Social consequences of manufactured longevity.

The signs are that advances in biomedical sciences will add more years of "manufactured time" to life expectancy in industrialised countries, resulting in unprecedented rates of survival into older ages. Increasing longevity will force economic and social changes and the 20th-century revolution in social roles looks set to continue into the 21st century.

Humans↗

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