The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.     

Individual Differences in Impulsive Action Reflect Variation in the Cortical Serotonin 5-HT2A Receptor System

Impulsivity is an important feature of multiple neuropsychiatric disorders, and individual variation in the degree of inherent impulsivity could play a role in the generation or exacerbation of problematic behaviors. Serotonin (5-HT) actions at the 5-HT_2AR receptor (5-HT_2AR) promote and 5-HT_2AR antagonists suppress impulsive action (the inability to withhold premature responses; motor impulsivity) upon systemic administration or microinfusion directly into the medial prefrontal cortex (mPFC), a node in the corticostriatal circuit that is thought to play a role in the regulation of impulsive action. We hypothesized that the functional capacity of the 5-HT_2AR, which is governed by its expression, localization, and protein/protein interactions (eg, postsynaptic density 95 (PSD95)), may drive the predisposition to inherent impulsive action. Stable high-impulsive (HI) and low-impulsive (LI) phenotypes were identified from an outbred rodent population with the 1-choice serial reaction time (1-CSRT) task. HI rats exhibited a greater head-twitch response following administration of the preferential 5-HT_2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and were more sensitive to the effects of the selective 5-HT_2AR antagonist M100907 to suppress impulsive action relative to LI rats. A positive correlation was observed between levels of premature responses and 5-HT_2AR binding density in frontal cortex ([³H]-ketanserin radioligand binding). Elevated mPFC 5-HT_2AR protein expression concomitant with augmented association of the 5-HT_2AR with PSD95 differentiated HI from LI rats. The observed differential sensitivity of HI and LI rats to 5-HT_2AR ligands and associated distinct 5-HT_2AR protein profiles provide evidence that spontaneously occurring individual differences in impulsive action reflect variation in the cortical 5-HT_2AR system.     

Interferon gamma release assay in the diagnosis of tuberculous mastitis

Tuberculous mastitis is rare, especially in Western countries. We describe a case where the interferon gamma release assay blood test led to diagnosis and successful treatment of the disease.     

Prostate cancer detection upon transrectal ultrasound-guided biopsy in relation to digital rectal examination and prostate-specific antigen level: what to expect in the Chinese population?

We investigated the prostate cancer detection rates upon transrectal ultrasound (TRUS)-guided biopsy in relation to digital rectal examination (DRE) and prostate-specific antigen (PSA), and risk factors of prostate cancer detection in the Chinese population. Data from all consecutive Chinese men who underwent first TRUS-guided prostate biopsy from year 2000 to 2013 was retrieved from our database. The prostate cancer detection rates with reference to DRE finding and PSA level of < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ were investigated. Multivariate logistic regression analyses were performed to investigate for potential risk factors of prostate cancer detection. A total of 2606 Chinese men were included. In patients with normal DRE, the cancer detection rates were 8.6%, 13.4%, 21.8%, 41.7% and 85.2% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. In patients with abnormal DRE, the cancer detection rates were 12.4%, 30.2%, 52.7%, 80.6% and 96.4% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. Older age, smaller prostate volume, larger number of biopsy cores, presence of abnormal DRE finding and higher PSA level were associated with increased risk of prostate cancer detection upon multivariate logistic regression analyses (P < 0.001). Chinese men appeared to have lower prostate cancer detection rates when compared to the Western population. Taking the different risk factors into account, an individualized approach to the decision of TRUS-guided biopsy can be adopted.     

Grasping without vision: Time normalizing grip aperture profiles yields spurious grip scaling to target size

The analysis of normalized movement trajectories is a popular and informative technique used in investigations of visuomotor control during goal-directed acts like reaching and grasping. This technique typically involves standardizing measures against the amplitude of some other variable – most typically time. Here, we show that this normalizing technique can lead to some surprising results. In the first of two experiments, we asked participants to grasp target objects without ever seeing them from trial to trial. In the second experiment, participants were given a brief preview of the target and were then cued 3 s later to pick it up while vision was prevented. Critically, on some trials during the delay period and unbeknownst to the participants, the previewed target was swapped for a new unseen one. The results of both experiments show that time-normalized measures of grip aperture during the closing phase of the movement appear to be scaled to target size well before the fingers make contact with the target – even though participants had no idea what the size of the target was that they were grasping. In contrast, a classical measure of anticipatory grip scaling, maximum grip aperture, did not show scaling to target size. As we demonstrate, however, in both experiments, movement time was longer for the larger target than the smaller ones. Thus, the comparisons of time-normalized grip aperture, particularly during the closing phase of the movements, were made across different points in real time. Taken together, the results of these experiments highlight a need for caution when investigators interpret differences in time-normalized dependent measures – particularly when the effect of interest is correlated with the dependent measure and a third variable (e.g., movement time) that is used to standardize the dependent measure.     

Left handedness does not extend to visually guided precision grasping

In the present study, we measured spontaneous hand preference in a "natural" grasping task. We asked right- and left-handed subjects to put a puzzle together or to create different LEGO models, as quickly and as accurately as possible, without any instruction about which hand to use. Their hand movements were videotaped and hand preference for grasping in ipsilateral and contralateral space was measured. Right handers showed a marked preference for their dominant hand when picking up objects; left handers, however, did not show this preference and instead used their right hand 50% of the time. Furthermore, compared to right handers, left handers used their non-dominant hand significantly more often to pick up objects in ipsilateral as well as contralateral space. Our results show that handedness in left handers does not extend to precision grasp and suggest that right handedness for visuomotor control may reflect a universal left-hemisphere specialization for this class of behaviour.