The human SHIP gene is differentially expressed in cell lineages of the bone marrow and blood

The macrophage colony-stimulating factor receptor and several other hematopoietic growth factor receptors induce the tyrosine phosphorylation of a 145- to 150-kD protein in murine cells. We have previously cloned a cDNA for the murine 150-kD protein, SHIP, and found that it encodes a unique signaling intermediate that binds the SHC PTB domain through at least one tyrosine phosphorylated (NPXY) site in the carboxyl-terminal region. SHIP also contains several potential SH3 domain-binding sites, an SH2 domain for binding other tyrosine phosphorylated proteins, and an enzymatic activity that removes the phosphate from the 5 position of phosphatidylinositol 3,4,5-phosphate or from inositol 1,3,4,5-phosphate. SHIP has a negative effect on cell growth and therefore loss or modification may have profound effects on hematopoietic cell development. In this study, we have cloned a cDNA for human SHIP and examined mRNA and protein expression of SHIP and related species in bone marrow and blood cells. Flow cytometry indicates that at least 74% of immature CD34+ cells express SHIP cross-reacting protein species, whereas within the more mature population of CD33+ cells, only 10% of cells have similar expression. The majority of T cells react positively with the anti-SHIP antibodies, but significantly fewer B cells are positive. Immunoblotting detects up to seven different cross-reacting SHIP species, with peripheral blood mononuclear cells exhibiting primarily a 100-kD protein and a CD34+ acute myeloblastic leukemia expressing mainly 130-kD and 145-kD forms of SHIP. Overall, these results indicate that there is an enormous diversity in the size of SHIP or SHIP-related mRNA and protein species. Furthermore, the expression of these protein species changes according to both the developmental stage and differentiated lineage of the mature blood cell.     

A novel mutation of presenilin 1 in familial Alzheimer's disease in Israel detected by denaturing gradient gel electrophoresis

Germline mutations in the presenilin 1 (PS1) gene apparently account for the majority of early-onset, familial Alzheimer's disease (AD). Using a mutation-screening strategy (denaturing gradient gel electrophoresis; DGGE), we analyzed a large family with early onset AD and seizures. The patients in this family showed a novel missense mutation in exon 5 of the PS1 gene (A to T change in codon 120, altering glutamine to aspartic acid). This novel mutation is located within the second hydrophilic domain of the molecule, a region not particularly involved in previously described germline mutations, and is of unknown biological significance. These results also demonstrate that DGGE can be used effectively to screen for mutations within this gene.     

A stingray spine in the scapula of a bottlenose dolphin

A stingray spine was found lodged in the scapula of a deceased 272 cm, male bottlenose dolphin (Tursiops truncatus) from South Carolina (USA) following skeletal preparation, nearly 6 mo after necropsy. No external puncture wound, internal bruising, or laceration of muscle tissue surrounding the scapula was evident during necropsy of the animal. Implantation of the spine did not appear to be related to the death of the dolphin, but probably occurred at an early age. Abnormal development of bone surrounding the spine resulted in the formation of a cavity at the wound site. Two mechanisms were considered as contributors for the cavity formation. These were the mechanical action of the spine stimulating the body's defense system for managing foreign objects, and the release of potent toxins from the spine sheath.     

Neurobiology and sexual orientation: current relationships

Despite great progress in the neurosciences, our understanding of the determinants of sexual orientation is incomplete. The authors review for the clinician/neuropsychiatrist studies pertaining to the formation of sexual orientation in the following areas: hormone effects on sexual behavior (animal and human); the complicated relationship between gender identity, gender role, and sexual orientation in humans; cross-cultural studies of homosexuality; behavioral observations in pseudohermaphrodites and offspring of mothers treated with hormones during pregnancy; brain studies of homosexual and heterosexual individuals; and genetic studies. The authors conclude that human sexual orientation is complex and diversely experienced and that a biopsychosocial model best fits the current state of knowledge in the field.     

Cortical cholinergic impairment and behavioral deficits produced by kainic acid lesions of rat magnocellular basal forebrain.

The rat magnocellular basal forebrain (MNBF) is homologous to the human nucleus basalis of Meynert, a structure implicated in the cholinergic hypothesis of cognitive impairment in Alzheimer's disease (AD). In the present study, 18 male Sprague-Dawley rats with kainic acid lesions in the MNBF were compared with 6 unoperated controls, 10 sham-operated controls, and 6 controls injected with kainic acid in the cortical area directly above the MNBF. MNBF lesions depleted choline acetyltransferase in cortex but not in striatum or hippocampus. Cortical dopamine levels were unchanged; serotonin levels were unchanged in hippocampus and parietal cortex but decreased in frontal cortex. Compared with controls, MNBF-lesioned Ss were impaired in 24-hr retention, but not acquisition, of a passive avoidance task with escapable footshock. The groups did not differ in mean number of daily avoidances on a barpress active avoidance task, although learning was slower in MNBF-lesioned Ss. In a serial spatial discrimination reversal test, MNBF-lesioned Ss performed significantly worse than controls. This model may be useful for studying the role of the cholinergic system in memory and possibly for developing treatment strategies to alleviate the cognitive dysfunction of AD. (63 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An economic evaluation of the use of rare earth screens to reduce the radiation dose from diagnostic X-ray procedures in Israel

In Israel the diffusion of rare earth screen technology has been limited. These screens could halve the radiation dose to the patient from diagnostic X-ray radiography, with little managerial effort and without being detrimental to the quality of the diagnostic image. We estimated the total effective dose from diagnostic film radiography capable of reduction by the use of rare earth screens, based on the number of hospital and ambulatory diagnostic X-ray procedures. This number was multiplied by the computed radiation dose per body site for a series of diagnostic procedures. The annual dose was approximately 0.53 mSv per head, approximately half of which could be averted by the introduction of rare earth screen technology. Based on a fatality risk of 3% Sv-1, it is estimated that the adoption of rare earth screen technology might reduce the annual incidence of cancer by some 93 cases, half of which would be fatal after an average latency period of 18.4 years. The cost of purchasing rare earth screens on a nationwide basis is approximately $3.0 million. This cost is outweighed by a saving of $9.6 million in X-ray tube replacement costs over the period 1997-2006. Government legislation enforcing the use of rare earth screens is essential, because of the lack of prestige associated with acquiring rare earth technology, as well as institutional reluctance to accept the external benefits of reduced morbidity and mortality and/or to extend budgetary time horizons.     

IL-1 beta and TNF alpha modulate delta 9-tetrahydrocannabinol-induced catalepsy in mice

The role of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) in THC-induced catalepsy in mice was examined. Recombinant IL-1 beta (400 ng/mouse, IV) and TNF alpha (500 ng/mouse, IV) were effective in potentiating the cataleptic effect of low-dose THC (10 micrograms/mouse, IV). Recombinant IL-1 alpha and IL-6 did not potentiate catalepsy at any dose tested. Anti-IL-1 beta and anti-TNF alpha antibodies were effective in attenuating high-dose (75 micrograms/mouse) THC-induced catalepsy. Antibodies to IL-1 alpha and IL-6 had no effect on catalepsy. Early onset catalepsy (10 min postinjection) was potentiated by exogenous recombinant IL-1 beta and TNF alpha but only later catalepsy (2 h postinjection) was attenuated by antibodies to endogenous IL-1 beta or TNF alpha. This divergence of the cytokine effect suggests that these substances regulate, by different mechanisms, the early and late THC-induced cataleptic response.     

Correlates of fatigue in older women with heart failure

OBJECTIVE: To examine the relative contribution of psychologic factors and physical symptoms to the variance in fatigue in older women with heart failure. METHODS: Eighty women who had been hospitalized in the previous 12 months for heart failure were interviewed. Fifty-seven women completed second interviews 18 months after the first interview. RESULTS: Fatigue was the most frequently occurring physical symptom at both measurement times, and it significantly increased with time. Other physical symptoms contributed uniquely to the variance in fatigue at both measurement times, but psychologic factors did not. At time 1, sleep difficulties, chest pain, and weakness each explained unique variance in fatigue. At time 2, dyspnea was the only variable that explained unique variance in fatigue (9%). Dyspnea also explained a significant portion of the variance (7%) in time 2 fatigue, when time 1 fatigue was controlled. CONCLUSIONS: Fatigue in older women with heart failure is related more to other physical symptoms than psychologic factors.