DNA-PKcs: a T-cell tumour suppressor encoded at the mouse scid locus

Severe combined immunodeficiency (SCID) mice are defective in their ability to rearrange their variable (V), diversity (D) and joining (J) genetic elements to generate functional immunoglobulin (Ig) and T-cell receptor (TCR) molecules; as a result, they lack mature B and T cells. These mice are highly sensitive to ionizing radiation, suggesting that the product of the scid gene plays a critical role in both V(D)J recombination and DNA double-strand break repair. Recent studies suggest that the SCID defect lies in the gene encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PK; refs 6-8), a nuclear protein made up of the Ku 70 and Ku 86 subunits as well as the large catalytic subunit, DNA-PKcs. Other reports have implied that the SCID phenotype correlates with nonsense mutations at the extreme 3' end of Prkdc, the DNA-PKcs gene. The identity of the gene remains in doubt, however, because the consequences of genetic inactivation of Prkdc have not been determined. This study shows that complete inactivation of Prkdc in a novel insertional mouse mutant recapitulates the SCID phenotype and that Prkdc and scid are alleic. Significantly, DNA-PKcs null mice demonstrate complete penetrance of thymic lymphoblastic lymphomas, strongly suggesting that Prkdc functions in mice as a T-cell tumour suppressor and, by virtue of its association with DNA repair and recombination, belongs to the 'caretaker' class of tumour-suppressor genes that includes ATM, BRCA1 and BRCA2 (ref. 15).     

Effects of pregnancy on hemoglobin AIc in normal, gestational diabetic, and diabetic women

Hemoglobin AIc, a normal minor hemoglobin, has glucose linked by a Schiff base to the N-terminal end of the beta chain. The glucose interferes with the binding of 2,3 diphosphoglycerate, probably resulting in an increased affinity of that hemoglobin for oxygen. Hb AIc is increased to twice normal levels in juvenile-onset (insulin-dependent) diabetes. In the present studies, the Hb AIc, when expressed as per cent of total hemoglobin, was found to be elevated slightly in pregnany normal (m = 6.97 per cent), pregnant nondiabetic obese (m = 6.89 per cent), and gestationally diabetic subjects (m = 8.77 per cent) above that of normal females (m = 5.68 per cent). A remarkable difference was observed between the nonpregnant diabetics (m = 12.77 per cent) and the pregnant diabetics (m = 8.46 per cent). This decrease in the level of Hb AIc in diabetics who are pregnant more than 30 weeks may reflect either a better state of diabetic control and/or a compensatory mechanism to protect the fetus by facilitating oxygen exchange from mother to fetus.     

Validity of the Luria-Nebraska Neuropsychological Battery.

D. Delis and E. Kaplan (see record 1983-24742-001) criticized the Luria-Nebraska Neuropsychological Battery for not meeting some assumptions of content validity and, by inference, construct validity. Delis and Kaplan also criticized C. J. Golden for advocating improper use of the test battery as a substitute for clinical training and knowledge. The present authors evaluate the major points of Delis and Kaplan, indicating which are cogent to the battery and which are based on misunderstandings of the manner in which the battery should be used. The theoretical structure of the scales of the battery is briefly described, as are approaches to interpretation. Studies indicating that the battery has validity as a neuropsychological test and the requirements needed for accurate application of the battery are examined. (13 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Postintubation tracheal stenosis

Cryopreservation techniques for umbilical cord blood (UCB) have been based on methods established for marrow (BM) and peripheral blood progenitor cells (PBPC) with varying degrees of success. The aim of this study was to optimise cryopreservation of UCB haemopoietic cells based on sound cryopreservation principles. UCB samples were cryopreserved with different combinations of DMSO and hydroxyethyl starch (HES) by a variety of freezing protocols. After cooling at 1 degree C/min in solutions containing 4% HES and various concentrations of DMSO there was a dramatic fall in CD34+ recovery from 85.4% (s.d. 28.4) to 12.2% (s.d. 10.0) as DMSO concentration was reduced from 5 to 2.5%. Varying HES concentration in solutions containing 5% DMSO did not have a significant effect on CD34+ cell recovery. Increasing cooling rate from 1 to 10 degrees C/min significantly reduced CD34+ recovery (P < 0.0001) while increasing DMSO concentration up to 10% had little effect (P = 0.8, two-way ANOVA). Good recovery of UCB CD34+ cells can be achieved with 5-10% DMSO at a controlled cooling rate of 1 degrees C/min. There was a significant difference (P < 0.0001) in the apparent recovery of CD34+ cells between paired aliquots thawed in the presence (recovery = 76.8%, s.d. 26.0) and absence (32.5%, s.d. 18.7) of DNase. In conclusion, conditions for cryopreserving UCB for clinical banking that yield optimal recovery of CD34+ cells have been established.     

The synthesis of prostaglandin analogs containing the (hydroxycyclooctylidene)methyl ring system

The synthesis of prostaglandin analogs incorporating the (2-hydroxycyclooctylidene)methyl moiety in place of the natural C13-C20 sidechain has been accomplished via copper-assisted conjugate addition of the (cyclooctylidene)methyllithium 5 to the cyclopentenone intermediates 7 and 10.     

On “The shallow water equations” By M. Shinbrot

Summary The paper [1] above describes two steady shallow water flows which differ from the known flows of this type. It is suggested that the conditions imposed in obtaining these solutions are not consistent.     

Relaxin immunoactivity in human plasma during a 24-hr period

The effects of methionine, cysteine and serine on the rate and strength of contractions of isolated Langendorff preparations of perfused dog heart and on spontaneous release of catecholamine (CA) from these hearts were investigated. These neutral amino acids increased the amplitude of ventricular contractions. Methionine and cysteine also stimulated the ventricular rate. They induced release of noradrenaline (NA) from the isolated heart. Their inotropic and chronotropic effects were significantly inhibited by pretreatment of the heart with propranolol.