A new detector for fully automatic peptide synthesis

A new method of monitoring the rate of reactions in solid phase peptide synthesis is described. A conductivity detector in the reaction cell enables the deprotection, washing, and subsequent coupling stages to be examined in detail. The half lives of the reactions can be calculated and hence the optimum reaction times predicted. The aggregation of peptide chains and subsequent collapse of the resin is observed. Difficult sequences are sensed and appropriate action taken completely automatically.     

COLON CANCER AND POLYPS IN ACROMEGALY: INCREASED RISK ASSOCIATED WITH FAMILY HISTORY OF COLON CANCER

A cohort of 52 subjects diagnosed with acromegaly in southeastern Michigan and northern Ohio between 1935 and 1985 were followed to determine the incidence of colon cancer and polyps. Medical records were reviewed, subjects or their next-of-kin were interviewed, and screening examinations of the colon were offered to the living patients who were located. Data on demographics, personal histories of cancer and colon polyps, family history of colon cancer, and cure from acromegaly were obtained for both living and deceased subjects. The risk for colon cancer compared to the general population was estimated using standardized incidence ratios (SIRs). The expected number of cases was determined utilizing age, sex and race-specific rates provided by the cancer registry in southeastern Michigan. Among the 52 subjects, one could not be located and nine were deceased, none from colon cancer, with one known to have a history of colon polyps. Of 13 (31%) who declined the screening physical, one had a history of polyps and none reported a history of colon cancer. Two of 29 screened patients were found to have right-sided adenocarcinoma of the colon. Of the entire cohort, eight people (including one deceased) had a current or previous diagnosis of polyps, with five known to be histologically adenomatous. The SIR for colon cancer was 4.7 (95% confidence interval 0.6-17.1). Seven subjects, including the two with detected adenocarcinoma and four of the six living subjects with polyps only, reported a family history of colon cancer. The SIR for the subset of subjects with a family history of colon cancer was 29.1 (95% confidence interval of 3.5-104.6).(ABSTRACT TRUNCATED AT 250 WORDS)     

Teratology Study in Rats with Amsacrine, an Antineoplastic Agent

Teratology Study in Rats with Amsacrine, an Antineoplastic Agent.ANDERSON, J. A., PETRERE, J. A., SAKOWSKI, R., FITZGERALD, J.E., AND DE LA IGLESIA, F. A. (1986). Fundam. Appl. Toxicol.7, 214–220. Amsacrine, an acndinylamino derivative usedin the treatment of refractory leukemias, was evaluated forits teratogenic potential in pregnant rats. The compound wasgiven by intrapentoneal (ip) administration on Days 6 to 9 ofgestation to groups of 20 female CD rats at levels of 0.5, 1.0,and 2.0 mg/kg. Appropriate vehicle and untreated controls wereincluded. Dams given 2.0 mg/kg lost weight during and afterthe treatment period. Food consumption was comparable to controlsat all dose levels except for the high dose group in the post-treatmentperiod. Decreased litter size, increased postimplantation loss,and reduced fetal weights occurred with doses of 2.0 mg/kg.Significantly reduced fetal body weight and increased incidenceof stunting were the only adverse findings at 0.5 and 1.0 mg/kg,respectively. Two fetuses at 2.0 mg/kg, one at 1.0 mg/kg, oneat 0.5 mg/kg, and two vehicle control fetuses had gross abnormalities.Fetotoxicity, manifested by inhibition of osteogenesis and minorskeletal abnormalities, occurred with doses of 0.5 mg/kg ormore. The results indicate that amsacrine was embryolethal torats at doses of 2.0 mg/kg and embryotoxic at lower dose levels.Teratogenicity was not evident at doses which did not affectfetal survival.     

Chemical synthesis of a neurotoxic polypeptide from the sea anemone Stichodactyla helianthus+

The sea anemone Stichodactyla helianthus neurotoxin I, a 48-residue polypeptide, was synthesized by automated solid phase methodology. The fully reduced polypeptide was subsequently refolded in the presence of a glutathione oxidoreduction buffer to the biologically active species containing three disulfide bonds. The overall yield after rigorous purification was 12.5%. The circular dichroism (CD), and proton nuclear magnetic resonance (¹ H NMR) spectra of the HPLC-purified synthetic toxin were indistinguishable from those obtained concurrently with the natural toxin. A subtilisin digest of the synthetic neurotoxin generated peptide fragments identical to that of a sample of the natural toxin subjected to the same treatment. The toxicity of the synthetic polypeptide was identical to that of the natural toxin (crab LD₅₀, 3.1μg/kg). The equilibrium dissociation constant (28 nM) for interaction of the synthetic toxin with crab axolemma vesicles was nearly identical to that of the natural toxin (25 nM).     

Increased severity of alcohol withdrawal in in-patient alcoholics with a co-existing anxiety diagnosis

The purpose of this study was to determine whether alcoholics with a co-existing anxiety disorder (dual-diagnosed group) experienced different withdrawal symptomatology from alcoholics without an anxiety disorder (alcohol-only group). Symptoms of alcohol withdrawal were measured on admission to an in-patient treatment program and throughout treatment (days 0, 2, 7, 14 and 21) using the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. The dual-diagnosed group exhibited more severe alcohol withdrawal, as indicated by higher total CIWA-Ar scores, at all time points than the alcohol-only group. The possibility that anxiety disorders and alcohol withdrawal share a common neurochemical basis and that the CIWA-Ar scale may be useful as a screening instrument for anxiety disorders in alcoholics is discussed.     

QT Prolongation and Monomorphic VT Caused by Pheochromocytoma

Introduction: Pheochromocytoma may present with ECG abnormalities as one of the few clues to the diagnosis.
Methods and Results: A 30-year-old woman presented with chest pain and a QTc of 525 ms. Four weeks later following a syncopal episode, her QTc was 660 ms. Short runs of monomorphic ventricular tachycardia were recorded. Investigations revealed an adrenal pheochromocytoma. Her QTc normalized after excision of the tumor. Comprehensive QT gene screening of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 was negative.
Conclusion: Pheochromocytoma may induce monomorphic VT and QT prolongation. The interaction of different catecholamines may have a compounding effect on cardiac repolarization.