Effect of bombesin upon plasma somatostatin-like immunoreactivity, insulin and glucagon in normal and chemically sympathectomized dogs

The present study was designed to determine the effects of intravenously infused bombesin (10 ng/kg/min) upon basal and postprandial plasma somatostatin-like immunoreactivity (SLI), glucagon, insulin and triglyceride levels in normal (n = 12) and chemically sympathectomized (n = 11) dogs. Basal plasma SLI, glucagon and insulin levels rose significantly during the infusion of bombesin in the normal dogs, and this was not altered by chemical sympathectomy. Bombesin infusion enhanced the postprandial SLI response, while attenuating the postprandial glucagon response by 50% and the insulin response in the early postprandial phase of the meal. Sympathectomy did not significantly alter the basal levels of these polypeptides, but augmented the postprandial plasma SLI response during the first 90 min, and reduced the postprandial glucagon response during the infusion of bombesin. The postprandial insulin response was not affected by sympathectomy. In both normal and chemically sympathectomized dogs the rise in postprandial triglyceride levels was attenuated by bombesin infusion.     

Stem cells and immunological parameters in mice during the latency period and after the development of chemically induced leukemia

T-cell leukemias have been induced in adult BDF1 mice by 12 or 15 weeks of exposure to butylnitrosourea (BNU) in the drinking water. This led to a depression of CFU-S numbers and reduced T- and B-cell responses to mitogens. These parameters were then studied during the BNU-free preleukemic latency period in individual mice. At the same time, leukemic cells were traced in the thymus, the spleen, and the bone marrow by transplantation. In mice without leukemia and mice with leukemic cells in only one organ, there was a general tendency to normal CFU-S numbers and T- and B-cell responses with time after BNU, although control levels were reached in only a few of the mice. The reaction of mixed lymphocyte cultures (MLC) remained low during the latency period. In the thymus an imbalance of the Con A, PHA, and MLC responses was observed. Out of 25 mice with induced leukemia, 8 had leukemic cells in the thymus only and 2 in the marrow only. In mice with leukemic cells in all 3 hemopoietic organs and an enlargement of the spleen, a shift of CFU-S from the marrow to the spleen was observed.     

Combination of microdialysis and glucosensor permits continuous (on line) SC glucose monitoring in a patient operated device. II. Evaluation in animals.

The microdialysis technique was used for following the glucose content of the extracellular subcutaneous (SC) fluid under varying blood glucose levels in rats. The glucose content in the microdialysis perfusion fluid was continuously analyzed by means of the measuring flow chamber of an ex vivo glucose monitor. In six ChBB rats blood glucose levels were varied between 40 mg/dl and 575 mg/dl by intravenous (IV) infusion of glucose and by SC injections of insulin, respectively. After a running-in period of about half an hour, the glucose content in the perfusion fluid was closely related to the blood glucose concentration (r > 0.92) up to a time period of 6 hrs. The "relative recovery" rate of glucose by the microdialysis probe in the SC tissue varied within the 6 experimental sessions. The relative recovery rate could be shown to be not dependent on the absolute blood glucose levels in the individual rat within the glucose concentration range tested.     

Socially stimulated androgen surges in male hamsters: the roles of vaginal secretions, behavioral interactions, and housing conditions.

The sources of cues necessary for elicitation of androgen surges and sexual behavior in male golden hamsters (Mesocricetus auratus) were investigated. Circulating androgen levels were measured in males after interactions with other males or several types of estrous females: intact females, vaginectomized females, or vaginectomized females scented with vaginal secretions. All groups of males that interacted with estrous females demonstrated significant elevations in androgens whereas those that interacted with other males did not. Thus, the presence of vaginal secretions is not necessary for the elicitation of androgen surges in sexually experienced male hamsters. Individual differences in sexual performance were not correlated with the degree of change in androgen levels, suggesting that such hormonal responses are not graded but are all-or-none. Housing males in isolation from females did not alter either baseline androgen levels or the magnitude of androgen responses caused by interactions with females.     

Carbohydrate structure of a thrombin-like serine protease from Agkistrodon rhodostoma. Structure elucidation of oligosaccharides by methylation analysis, liquid secondary-ion mass spectrometry and proton magnetic resonance.

The carbohydrate side chains of the thrombin-like serine protease ancrod from the venom of the Malayan pit viper Agkistrodon rhodostoma were liberated from tryptic glycopeptides by treatment with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F and fractionated by high-performance liquid chromatography. Glycans obtained were characterized by digestion with exoglycosidases, methylation analysis and, in part, by liquid secondary-ion mass spectrometry and 1H-NMR spectroscopy. The results reveal that this snake venom glycoprotein contains partially truncated di-, tri- and tetraantennary complex type N-glycans carrying Fuc(alpha 1-6) residues at the innermost N-acetylglucosamine and solely (alpha 2-3)-linked sialic acid substituents. As a characteristic feature, ancrod oligosaccharides comprise mainly sialylated Gal beta 3GlcNAc beta lactosamine antennae. Furthermore, a small proportion of the sugar chains were found to carry a NeuAc alpha 3GalNAc beta 4GlcNAc beta antenna exclusively linked to C-2 of Man(alpha 1-3) residues of the pentasaccharide core. Thus, many of the glycans found represent novel glycoprotein-N-glycan structures.     

Reproductive toxicity with and without LHRHA administration during adjuvant chemotherapy in patients with germ cell tumors.

In order to evaluate the protective efficacy of an agonist of luteinizing hormone releasing hormone (LHRHA) on spermatogenic stem cells, we undertook a prospective study in patients with germ cell tumors. Following orchiectomy and unilateral lymph node dissection all patients received adjuvant chemotherapy consisting of 2 courses of PVB regimen (cisplatin, vinblastine and bleomycin). Six men were treated with LHRHA (d-Ser-(TBU)6 LHRH ethylamide) before, during and after PVB chemotherapy. Eight patients without LHRHA protection served as controls, receiving the identical chemotherapy. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were within normal limits before therapy in all patients. In 6/6 protected patients, serum levels of FSH, LH and testosterone were effectively suppressed during pre-chemotherapeutic LHRHA administration. All protected patients showed elevated serum FSH levels and azoospermia after cessation of chemotherapy and LHRHA treatment due to germ and stem cell loss. Median FSH level and sperm density of the protected group normalized within 24 months after chemotherapy. In all unprotected patients elevated FSH values and azoospermia also occurred after chemotherapy. Likewise, median FSH level and sperm density normalized spontaneously in this group within 24 months after chemotherapy. Our results suggest completely reversible reproductive toxicity two years after 2 courses of adjuvant chemotherapy in all patients. Administration of LHRHA during chemotherapy seems to have no protective effects on germ cells since both groups developed reproductive toxicity. Furthermore, recovery time was identical in the protected and unprotected patients. FSH and LH could be used as diagnostic markers to assess the degree and duration of reproductive and endocrine gonadal toxicity after chemotherapy.     

General features in the stoichiometry and stability of ionophore A23187-cation complexes in homogeneous solution

Existing literature describing the stoichiometry and stability of complexes between A23187 and divalent cations in solution has been extended to include additional transition series cations, the heavy-metal cations Cd2+ and Pb2+, plus seven lanthanide series trivalent cations. Stability constants of 1:1 complexes between the ionophore and the divalent cations vary by 6.2 orders of magnitude between Cu2+ and Ba2+ which are the strongest and weakest complexes, respectively. Considering alkaline-earth and first-series transition cations together, the pattern of stability constants obeys the extended Irving-Williams series as is seen with many nonionophorous liganding agents. Cd2+ and Pb2+ are bound with an affinity similar to those of Mn2+ and Zn2+, whereas the lanthanides are bound with little selectivity and slightly higher stability. Titration of the ionophore in the 10(-5) M concentration range with di- and trivalent cations gives rise first to complexes of stoichiometry MA2 and subsequently to MA as the metal concentration is increased. The second stepwise stability constants for formation of the MA2 species exceeds the first constant by approximately 10-fold. With lanthanides, heavy metals, and transition-metal cations, OH-, at near physiological concentrations, competes significantly with free ionophore for binding to the 1:1 complexes. This competition is not apparent when Ca2+ or Mg2+ are the central cations. Possible implications of the 1:1 complex selectivity pattern, the ionophore-hydroxide competitive binding equilibria, and potential ternary complexes involving 1:1 ionophore:cation complexes and other anions present in biological systems are discussed with respect to the ionophore's transport selectivity and biological actions.     

Immunochemical analysis of the carbohydrate moiety of yeast killer toxin K28

Killer toxin K₂₈, a 16 kd protein secreted by the wine yeast Saccharomyces cerevisiae strain 28, was reversibly bound by a column of Concanavalin A-Sepharose, confirming its glycoprotein nature. HPLC analysis of acid hydrolyzates of K₂₈ toxin as well as Western-blots of -eliminated and/or endo H-treated killer toxin preparations probed with polyclonal -toxin antibodies revealed that the carbohydrate moiety of K₂₈ consists of D-mannose only, which is O-glycosidically linked via Ser/Thr residues to the protein part. The change in gel mobility of K₂₈ after -elimination was caused by a decrease in molecular mass of about 1,800, corresponding to a carbohydrate moiety of 10 mannose residues per killer toxin molecule.     

Mirror image duplications of chromosome 21. Three new cases and discussion of the mechanisms of origin

Summary Three new cases of mirror image duplication of a chromosome 21 are studied. In the first case the extra chromosome derived from a single paternal chromosome 21 by intrachromosomal interchange. The analysis of similar published cases suggests that this mechanism may predominate, but interchromosomal interchange, para- and pericentric inversion are likely as well.