The Philadelphia chromosome in acute leukemia.

The cytogenetics, cytology and cytochemistry, clinical findings, therapeutic response and survival of patients presenting with acute leukemia and the Philadelphia chromosome (Ph1) are briefly reviewed based upon a survey of the world literature and 16 cases seen at the University of Minnesota during the last 10 years. Details regarding the 16 cases from the University of Minnesota series are presented and two appendices listing the majority of reports of Ph1 + acute leukemia are included. Comparison of adults with Ph1+ and Ph1- acute leukemia demonstrate important clinical, therapeutic and prognostic differences. In general, patients with Ph1+ acute leukemia respond less well to treatment and survive significantly shorter periods of time. Since the presence of the Philadelphia chromosome in acute leukemia has therapeutic and prognostic significance, marrow chromosome studies should be performed in adults presenting with acute leukemia, especially acute lymphocytic leukemia.     

ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class I assembly.

The assembly of newly synthesized MHC class I molecules within the endoplasmic reticulum and their association with the transporter associated with antigen processing (TAP) is a process involving the chaperones calnexin and calreticulin. Using peptide mapping by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to identify a new component, we now introduce a third molecular chaperone, the thiol-dependent reductase ER-60 (ERp57/GRP58/ERp61/HIP-70/Q2), into this process. ER-60 is found in MHC class I heavy chain complexes with calnexin that are generated early during the MHC class I assembly pathway. The thiol reductase activity of ER-60 raises the possibility that ER-60 is involved in the disulfide bond formation within heavy chains. In addition, ER-60 is part of the late assembly complexes consisting of MHC class I, tapasin, TAP, calreticulin and calnexin. In a beta2-microglobulin (beta2m)-negative mouse cell line, S3, ER-60-calnexin-heavy chain complexes are shown to bind to TAP, suggesting that beta2m is not required for the association of MHC class I heavy chains with TAP.     

Bone mineral content in normally menstruating women with hyperprolactinaemia

Decreased bone density has been reported in women with hyperprolactinaemia due to pituitary tumours. We identified a number of seemingly healthy women with hyperprolactinaemia, i.e. a serum prolactin concentration exceeding 500 mU/l (25 micrograms/l) on three occasions, during a study in 1980/1981 of a representative population sample of greater than 1,400 women in seven different age strata (range 26-72 years). We compared vertebral bone mineral content and bone mineral areal content in 5 hyperprolactinaemic normally menstruating 50-year-old women with that of 6 controls matched for age and menstrual status but found no difference. Since the degree of prolactin elevation was similar in our study group to that previously reported for hyperprolactinaemic subjects with pituitary tumours and the time of exposure to raised hormone concentration appears to be of the same magnitude, other hormonal changes than hyperprolactinaemia per se seem to be the cause of low bone mineral content in women with hyperprolactinaemia and amenorrhoea.     

Cytotoxic T lymphocyte (CTL)-mediated cytolysis proceeds in the absence of Na+/H+ antiport activity: regulation of cytosolic pH by the Na+/H+ antiport in a cloned CTL.

Cytotoxic T lymphocyte (CTL)-mediated cytolysis of specifically bound target cells (TC) is thought to be triggered by cross-linking the T-cell antigen receptor (TcR). Biochemical events associated with TcR cross-linking include increased intracellular calcium levels [Ca2+]i, hydrolysis of phosphatidylinositol (PI), and an increase in intracellular pH [pH]i. Whereas CTL-mediated cytolysis of some TC is calcium-dependent, and PI hydrolysis is speculated to trigger the CTL lethal hit via activation of PKC, little is known about changes in [pH]i relating to activation of the lethal hit stage. We report regulation of [pH]i in a cloned CTL by the electroneutral Na+/H+ antiport during activation with PMA and specific antigen-bearing TC. Furthermore, using 5-(N-methyl-N-isobutyl) amiloride (MIBA), a potent antiport inhibitor, we demonstrate that Na+/H+ exchange is not required for activation of CTL cytolytic activity.     

On learning and living in holes by mantis shrimp

Mantis shrimp (Stomatopoda, Crustacea) that normally occupy holes in coral were presented with novel burrows (Erlenmeyer flasks painted black) in the laboratory. Individuals learn to recognize characteristics of the flask and enter, the burrow increasingly rapidly with repeated exposure to the flask. Individuals show consistently fast or slow learning curves, suggesting individual differences in learning ability. Three to seven days appears to be a critical period during which the stimulus must be re-encountered, or else the response is partially forgotten. However, a partial response remains after 14 days, and subsequent re-exposure to the stimulus is associated with more rapid re-acquisition of the entry behaviour than in naive animals. Field observations support the interpretation that individuals learn characteristics of their burrows and the environment. Further studies are needed to investigate the relationship of learning ability to the ritualized behaviour repertoire and to social interactions.     

Benzamidomethaneboronic acid: synthesis and inhibition of chymotrypsin

Benzamidomethaneboronic acid (2) has been synthesized unambiguously from the reaction of dibutyl iodomethaneboronate and N-lithiohexamethyldisilazane to form dibutyl [bis(trimethylsilyl)amino]methaneboronate (4), which was desilylated, benzoylated, and hydrolyzed to 2. It has been shown that 2 is a strong competitive inhibitor of alpha-chymotrypsin (Ki = 8.1 X 10(-6) M, pH 7.5). The reaction product from dibutyl iodomethaneboronate and sodiobenzamide, previously shown to be a potent inhibitor of chymotrypsin, was shown by this work to be O-linked isomer, benzimidoxy-methaneboronic acid (3). The pH-Ki profile over the pH range 6.5-9.5 was consistent with the formation of an enzyme-inhibitor complex which resembled the metastable tetrahedral reaction intermediates occurring during acylation and deacylation of chymotrypsin-catalyzed hydrolysis.     

Membranolytic and nucleolytic activities of cytolytic T lymphocyte clones

In an attempt to see if the nucleolytic and membranolytic activities of cytolytic T lymphocytes (CTL) were totally independent and could be expressed independently, we cloned CTL and determined their membranolytic and nucleolytic activities. If the two lytic mechanisms were completely independent and could be independently expressed by individual CTL, we anticipated that we would find CTL clones exhibiting only one or the other activity. Initial examination of membranolytic and nucleolytic activities in 99 newly established CTL clones revealed a poor correlation (r = 0.4) between the two activities. In addition, some clones expressed membenolytic activity without nucleolytic activity, and others, nucleolytic activity without membenolytic activity. The results suggest that CTL have 2 or more separate and independent mechanisms that lead either to the membranolytic or to the nucleolytic lesions in target cells.     

Manipulation of objects in a captive group of lion-tailed macaques (Macaca silenus)

The purpose of this study was to investigate the manipulative propensities of a captive group of lion-tailed macaques (Macaca silenus). Simple natural objects (browse and bamboo poles) were provided regularly in the home cage. Findings indicate richness in the frequency and form of manipulative activities, with juvenile males manipulating the test objects more frequently and exhibiting more goal-directed manipulative activity than adult females. A variety of goal-directed manipulative activities (use of objects to act as ladders, to apply leverage, and to create perches) occurred spontaneously, with some instances involving joint action or social use. These data are consistent with the hypotheses that macaques possess extensive capacities for object exploration and social facilitation, and that an evolutionary history of omnivorous foraging habits correlates positively with the expression of anomalous sensorimotor skills.     

Biomechanical and neurophysiological studies on audition in eared and earless harlequin frogs (Atelopus)

Tissue displacement of various body surfaces and the auditory midbrain sensitivities to sound were measured in Atelopus species with or without a tympanic middle ear (“eared” and “earless”, respectively). Tissue displacement (vibration) of body regions was measured by laser Doppler vibrometer . The body wall directly overlying the lung is most dramatically displaced by sound pressure in all species tested. The otic (lateral head) region showed low displacement in earless species, but significant displacement to high-frequency sound in eared species. Peak tissue displacement of the body wall occurred within the frequency range of each species' advertisement vocalization. Peak tissue displacement of the otic region of the eared species also occurred within these frequencies. Multi-unit neurophysiological recordings of the auditory midbrain (torus semicircularis) also were obtained. Auditory sensitivity curves showed three distinct regions of sensitivity at low, middle, and high frequencies, the latter located within the frequency range of each species' advertisement vocalization. The correlation between auditory midbrain sensitivity and tissue displacement of the body wall region at advertisement vocalization frequencies, suggests that the body wall/lungs serve as the route of sound transfer to the inner ear in earless species and possibly in the eared species as well. Accepted: 4 April 1998