Application of a multi-turn time-of-flight mass spectrometer, MULTUM II, to organic compounds ionized by matrix-assisted laser desorption/ionization.

The circuit shape of the ion path, or the multi-turn, provides a solution for achieving unrestricted mass resolution from time-of-flight mass analyzers. The potential of a multi-turn type mass spectrometer, the MULTUM II, with a 1.308 m circuit controlled by four toroidal electric sector fields in biological applications was examined. With matrix-assisted laser desorption/ionization, the ion flight of 18 cycles gave a mass resolution of 10,000 for MH+ of protophorphyrin IX. This resolution was correlated with the flight length, and a resolution of 61,000 was achieved for MH+ of angiotensin I after 75 cycles or a 98.75 m total flight. The results demonstrate that the multi-turn mass spectrometer allows not only high resolution but also very high separation of the ions of molecular species from organic compounds.

Multi-turn time-of-flight mass spectrometers with electrostatic sectors.

The mass resolution of a time-of-flight (TOF) mass spectrometer is directly proportional to its total flight pathlength. Multi-turn or multi-passage ion optical geometries are necessary to obtain fight distances of sufficient length within reasonable size limitations. We have investigated ion optics for a multi-turn TOF mass spectrometer with electrostatic sectors. The concept of 'perfect' focusing conditions is introduced. Furthermore, a new type of multi-turn TOF mass spectrometer, the MULTUM Linear plus, was developed. It consists of four cylindrical electric sectors and 28 electric quadrupole lenses. It has a vacuum chamber 60 x 70 x 20 cm in size. Mass resolution is demonstrated to increase according to the number of ion cycles. A mass resolution of 350 000 (m/z = 28, FWHM) was achieved after 501.5 cycles. The MULTUM Linear plus analyzer is not simple, however; 28 electric quadrupole lenses are used. In order to reduce the number of ion optical parts, an improved multi-turn TOF mass spectrometer, the MULTUM II, consisting of only four toroidal electric sectors, was also developed. The possibility of tandem mass spectrometric applications using multi-turn TOF mass spectrometers is also discussed.

[Endocrine profiles and gonadotropin response to Gn-RH of men with testicular cancer].

PURPOSE: To investigate the function of the hypothalamic-pituitary-testicular axis in testicular germ cell tumors, we evaluated gonadotropin responses to gonadotropin-releasing hormone (Gn-RH), semen quality, and serum levels of sex steroid hormones in patients with testicular cancer. PATIENTS AND METHODS: Basal serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and human chorionic gonadotropin-beta (hCG-beta) were measured before and after high orchiectomy in 20 patients with germ cell tumors of the testicle (9 with seminoma and 11 with nonseminomatous tumor). Semen quality and basal serum levels of testosterone, free testosterone, and estradiol were measured before orchiectomy. The Gn-RH test was performed before orchiectomy in all patients and after orchiectomy in patients without detectable gonadotropin levels in pre-operative serum samples. Gonadotropin levels were measured at 0, 30, 60, 90, and 120 minutes after intravenous injection of 100 micrograms of luteinizing hormone-releasing hormone (LH-RH). RESULTS: Serum gonadotropin concentrations were not detectable in 6 of 8 (75%) men with hCG positive tumors or in 4 of 12 (33.3%) men with hCG negative tumors before orchiectomy. Before surgery, 10 men without detectable gonadotropin levels showed complete suppression of the LH and FSH responses to LH-RH and 10 men with detectable gonadotropin levels showed significant increases in the LH and FSH responses (p < 0.01) at 30 minutes. After surgery, the Gn-RH test was performed in 9 men without detectable gonadotropin levels prior to surgery. Seven of these 9 men exhibited significant increases in the LH and FSH responses (p < 0.01) at 30 minutes while no response to LH-RH before or after surgery was seen in 2 men with detectable serum hCG-beta. We observed a significantly lower sperm density (median 7.5 x 10(6)/ml, range 0.4 to 17.8) in men with hCG positive tumors than in men with hCG negative tumors (median 33 x 10(6)/ml, range 0 to 103) (p < 0.002). Although testosterone levels did not differ significantly in men with hCG positive tumors and men with hCG negative tumors, free testosterone levels were significantly higher in men with hCG positive tumors (median 28.4 ng/ml, range 8.5 to 39.8) compared with men with hCG negative tumors (median 18.7 ng/ml, range 4.9 to 24.1) (p < 0.002). Estradiol levels were significantly increased in men with hCG positive tumors (median 44 pg/ml, range 26 to 110) compared with men with hCG negative tumors (median 33.5 pg/ml, range 10 to 87) (p = 0.002). CONCLUSION: The present findings indicate that serum hCG producing testicular cancers are associated with a complete suppression of the gonadotropin response to Gn-RH at the pituitary level, resulting in an inhibition of LH and FSH secretion, and also that serum hCG secreted by testicular cancers may suppresses spermatogenesis and may stimulate androgen and estradiol production by the testes. Since suppressed serum gonadotoropin levels are found in men with hCG non-producing testicular cancers, other factors derived from the tumor may cause downregulation of the gonadotropin response to Gn-RH.