Cryptic ins(4;11)(q21;q23q23) detected by fluorescence in situ hybridization: a variant of t(4;11)(q21;q23) in an infant with a precursor B-cell acute lymphoblastic leukemia report of a second case

We report the chromosomal findings in a 4-year-old female with precursor B-cell acute lymphoblastic leukemia (ALL). The diagnostic karyotype showed an isochromosome 7q, i(7)(q10), as well as questionable rearrangements on 9p and 11q. Fluorescence in situ hybridization (FISH) studies on both interphase and metaphase cells using the MLL "break-apart" and the centromeric chromosome 4 probes were instrumental in the characterization of an MLL gene rearrangement, which was cryptic by conventional cytogenetic analysis. Specifically, the FISH pattern was consistent with an insertion of the 5' region of the MLL gene into chromosome 4 at band q21, most likely a variant t(4;11)(q21;q23). This is the second case of FISH detection of an ins(4;11) in ALL. Our case exemplifies the importance of FISH in the further characterization of precursor B-cell ALL cases without any apparent prognostically significant chromosomal abnormalities.     

Evidence that oxytocin is a physiological component of LH regulation in non-pregnant women

BACKGROUND: Regulation of the LH surge is central to the functioning of the female ovulatory cycle. In animal models, oxytocin has been shown to alter LH activity. Oxytocin advanced the LH surge and, conversely, oxytocin receptor antagonists inhibited full production of the LH surge in rats. Few data exist on the possibility that oxytocin modulates LH in women. METHODS: Ten non-pregnant women participated in this study over two menstrual cycles. One cycle was a control cycle, and the other a trial cycle; the two were separated by at least one cycle. When the diameter of an ovarian follicle was >15 mm, a subject was allocated at random into either a control or treatment group. In a control cycle, volunteers received normal saline; in a treatment cycle, volunteers received an oxytocin antagonist (atosiban). RESULTS: For treatment cycles, the maximum LH concentration was significantly less than that in control cycles (42.1 +/- 6.2 versus 60.3 +/- 8.3 IU/l respectively; P < 0.05). Maximum FSH and estradiol concentrations were not significantly different between the two groups. CONCLUSIONS: The results indicated that inhibition of endogenous oxytocin affects the endocrinology of the ovulatory cycle in women, and strongly suggest that oxytocin has a role in the physiological processes of LH regulation.     

Mast cells at the host-pathogen interface: host-protection versus immune evasion in leishmaniasis

Infection of a susceptible host with Leishmania, a protozoan parasite, causes the disease leishmaniasis, which is characterized by neutrophil, eosinophil, macrophage, lymphocyte and mast cell infiltration into the infected tissue followed by parasite growth. Although the roles played by other cells in leishmaniasis are known, the role of mast cells remains to be ascertained. Here, we demonstrate that Leishmania regulates mast cell infiltration to the site of infection, mast cell production and mast cell function resulting in differential growth of the parasite in resistant (C57BL/6 or CBA/T6T6) and susceptible (BALB/c) macrophages. An interleukin-3-dependent augmentation in mast cell committed progenitors is observed in BALB/c but not in C57BL/6 mice during Leishmania infection. The mast cell supernatants inhibit IFN-gamma-dependent restriction of Leishmania growth in macrophages in BALB/c mice whereas the reverse phenomenon occurs in C57BL/6 mice. Our data reveals a different facet of host-pathogen interaction.     

Selective increases in regional brain glucocorticoid: a novel effect of chronic alcohol

The hypothalamo-pituitary-adrenal axis shows functional changes in alcoholics, with raised glucocorticoid release during alcohol intake and during the initial phase of alcohol withdrawal. Raised glucocorticoid concentrations are known to cause neuronal damage after withdrawal from chronic alcohol consumption and in other conditions. The hypothesis for these studies was that chronic alcohol treatment would have differential effects on corticosterone concentrations in plasma and in brain regions. Effects of chronic alcohol and withdrawal on regional brain corticosterone concentrations were examined using a range of standard chronic alcohol treatments in two strains of mice and in rats. Corticosterone was measured by radioimmunoassay and the identity of the corticosterone extracted from brain was verified by high performance liquid chromatography and mass spectrometry. Withdrawal from long term (3 weeks to 8 months) alcohol consumption induced prolonged increases in glucocorticoid concentrations in specific regions of rodent brain, while plasma concentrations remained unchanged. This effect was seen after alcohol administration via drinking fluid or by liquid diet, in both mice and rats and in both genders. Shorter alcohol treatments did not show the selective effect on brain glucocorticoid levels. During the alcohol consumption the regional brain corticosterone concentrations paralleled the plasma concentrations. Type II glucocorticoid receptor availability in prefrontal cortex was decreased after withdrawal from chronic alcohol consumption and nuclear localization of glucocorticoid receptors was increased, a pattern that would be predicted from enhanced glucocorticoid type II receptor activation. This novel observation of prolonged selective increases in brain glucocorticoid activity could explain important consequences of long term alcohol consumption, including memory loss, dependence and lack of hypothalamo-pituitary responsiveness. Local changes in brain glucocorticoid levels may also need to be considered in the genesis of other mental disorders and could form a potential new therapeutic target.     

Psychosocial health risk factors and resources of medical students and physicians: a cross-sectional study

Background  

Epidemiological data indicate elevated psychosocial health risks for physicians, e. g., burnout, depression, marital disturbances, alcohol and substance abuse, and suicide. The purpose of this study was to identify psychosocial health resources and risk factors in profession-related behaviour and experience patterns of medical students and physicians that may serve as a basis for appropriate health promoting interventions.     

The prognosis of a normal stress-only Tc-99m myocardial perfusion imaging study

Background  

Stress-only imaging saves time and radiation exposure, but apprehension remains about the reliability, diagnostic, and prognostic accuracy of a normal stress-only study. The objective of this study was to determine the prognosis of stress-only SPECT MPI in routine clinical practice.     

Reduced isotope dose with rapid SPECT MPI imaging: Initial experience with a CZT SPECT camera

Background  

Cardiac SPECT imaging needs to become shorter and use lower radiation doses to compete with other available noninvasive imaging modalities. Recently introduced cadmium zinc telluride (CZT) SPECT cameras have the potential to achieve both goals, but clinical experience is so far limited.     

Correlates of protection efficacy induced by vaccinia virus‐specific CD8+ T‐cell epitopes in the murine intranasal challenge model

The recent identification of a large array of different vaccinia virus‐derived CD8⁺ T‐cell epitopes offers a unique opportunity to systematically analyze the correlation between protective efficacy and variables such as kinetics of expression and function of viral proteins, binding affinity to MHC molecules, immunogenicity, and viral antigen processing/presentation. In the current study, 49 different H‐2^b restricted epitopes were tested for their ability to protect peptide‐immunized C57Bl/6 mice from lethal i.n. challenge with vaccinia virus. The epitopes varied greatly in their ability to confer protection, ranging from complete protection with minimal disease to no protection at all. The function or kinetics of the viral antigen expression did not correlate with protective efficacy. However, binding affinity partially predicted protection efficacy and ultimately epitope immunogenicity and recognition of infected cells offered the best correlation.     

Transgenic expression of survivin compensates for OX40‐deficiency in driving Th2 development and allergic inflammation

Survivin, an inhibitor of apoptosis family molecule, has been proposed as a crucial intermediate in the signaling pathways leading to T‐cell development, proliferation, and expansion. However, the importance of survivin to T‐cell‐driven inflammatory responses has not been demonstrated. Here, we show that survivin transgenic mice exhibit an increased antigen‐driven Th2 lung inflammation and that constitutive expression of survivin reversed the defective lung inflammation even in the absence of OX40 costimulation. We found that OX40‐deficient mice were compromised in generating Th2 cells, airway eosinophilia, and IgE responses. In contrast, OX40‐deficient/survivin transgenic mice generated normal Th2 responses and exhibited strong lung inflammation. These results suggest that OX40 costimulation crucially engages survivin during antigen‐mediated Th2 responses. These findings also promote the notion that OX40 costimulation regulates allergic responses or lung inflammation by targeting survivin thereby enhancing T‐cell proliferation and resulting in more differentiated Th2 cells in the allergic inflammatory response.     

Early adolescent outcomes of institutionally deprived and non-deprived adoptees. III. Quasi-autism

BACKGROUND: Some young children reared in profoundly depriving institutions have been found to show autistic-like patterns, but the developmental significance of these features is unknown. METHODS: A randomly selected, age-stratified, sample of 144 children who had experienced an institutional upbringing in Romania and who were adopted by UK families was studied at 4, 6, and 11 years, and compared with a non-institutionalised sample of 52 domestic adoptees. Twenty-eight children, all from Romanian institutions, for whom the possibility of quasi-autism had been raised, were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) at the age of 12 years. RESULTS: Sixteen children were found to have a quasi-autistic pattern; a rate of 9.2% in the Romanian institution-reared adoptees with an IQ of at least 50 as compared with 0% in the domestic adoptees. There were a further 12 children with some autistic-like features, but for whom the quasi-autism designation was not confirmed. The follow-up of the children showed that a quarter of the children lost their autistic-like features by 11. Disinhibited attachment and poor peer relationships were also present in over half of the children with quasi-autism. CONCLUSIONS: The findings at age 11/12 years confirmed the reality and clinical significance of the quasi-autistic patterns seen in over 1 in 10 of the children who experienced profound institutional deprivation. Although there were important similarities with 'ordinary' autism, the dissimilarities suggest a different meaning.