MR features of the substantia innominata and therapeutic implications in dementias

We measured the thickness of the substantia innominata using magnetic resonance imaging in 122 patients with Alzheimer's disease (AD), 31 patients with dementia with Lewy bodies (DLB) and 34 patients with vascular dementia (VaD), and examined the correlates of cognitive response to donepezil. Although all dementia groups showed significant atrophy of the substantia innominata compared to 28 age-matched controls, atrophy was greater in the DLB group, but less in the VaD group than the AD group. Mini-Mental State Examination score changes at 12 weeks after donepezil administration inversely and significantly correlated with the thickness of the substantia innominata in patients with AD (n=103, r=-0.43, p<0.0001) and in patients with DLB (n=24, r=-0.57, p<0.01), but not in patients with VaD (n=12, r=-0.22, p>0.1). There may be some differences in cholinergic impairment among AD, DLB and VaD, reflecting cholinergic neuropathology. Clinical response to cholinergic therapy may be partly attributable to damaged cholinergic neurons in AD and DLB, but not in VaD, suggesting differences in the therapeutic implication of cholinergic system degeneration.     

Malignant solitary fibrous tumor of the soft tissue: a cytogenetic study

We report on a case of a solitary fibrous tumor that developed in the thigh of an 82-year-old woman. The tumor was composed of areas of high-grade sarcoma and typical solitary fibrous tumor. Its karyotype was: 70,XXX,+X[4],+1[2],add(1)(p36)[4],add(1)[2],+2[4],-3[4],+6[4],add(6)(p11)x2[4],+7[4],+9[3],-11[4],-12[4],-13[4],add(13)(p11)x2[4],-14[4],+15[4],-16[3],-17[4],-19[4],+20,[4],+21[4],+22[2],+mar1x2[4][cp4].     

Characterization and diagnostic use of a recombinant single-chain antibody specific for the gp116 envelop glycoprotein of Yellow head virus

Yellow head virus (YHV) is an invertebrate nidovirus that can cause mass mortality of the cultured Penaeus monodon shrimp. A single-chain variable fragment (scFv) antibody directed against the gp116 envelop glycoprotein of YHV was constructed from hybridomas. Variable heavy (V(H)) and light (V(L)) chain genes were amplified from cDNA using antibody-specific primers, linked to generate a full-length gene via a standard peptide linker, ligated into the pET28a expression vector and transformed into E. coli. The expressed insoluble scFv antibody was solubilized, purified using immobilized metal affinity chromatography and rapid refolded; final yield 1-1.5 mg/l. Solid-phase non-competitive enzyme-linked immunosorbent assay (non-competitive ELISA) determined the affinity constant (K(A)) to be 3.34+/-0.38 x 10(8)l/mol. The sensitivity and specificity of scFv antibody was demonstrated by ELISA, dot blot and Western blot analysis. The detection limit determined by dot blot and indirect ELISA was 9 ng and 45 ng of purified YHV, respectively. Dot-blot assays revealed that the scFv antibody could detect YHV-infected shrimp at 24h post-infection and did not cross-react with White spot syndrome virus (WSSV) and Taura syndrome virus (TSV) proteins. The scFv antibody therefore might find application in rapid, simple and sensitive diagnostic tests to detect YHV in farmed shrimp.     

Complex translocations derived stepwise from standard t(15;17) in a patient with variant acute promyelocytic leukemia

We report the case of an elderly man with an acute promyelocytic leukemia variant carrying complex variant translocations. The Q-banded karyotype and spectral karyotyping method revealed a typical t(15;17), and two complex rearrangements caused by stepwise translocation derived from a typical t(15;17). Chromosomes 8 and 14 were related to these rearrangements. The patient received induction chemotherapy using all-trans retinoic acid and achieved complete remission. To our knowledge, a case with complex rearrangements, caused by apparent stepwise translocation, at diagnosis, has not been reported previously.     

Shift of motor activation areas during recovery from hemiparesis after cerebral infarction: a longitudinal study with near-infrared spectroscopy

Motor functional recovery after stroke may be attributable to cerebral reorganization. We used near-infrared spectroscopy, which measures non-invasively the changes in oxy- and deoxy-hemoglobin concentrations in response to neural activation, for monitoring cerebral activation in stroke patients, and investigated the longitudinal changes in functional laterality of activations in the primary sensorimotor cortex during unilateral audio-paced (1 Hz) hand movement. We examined five ischemic stroke patients (4 females and 1 male, 52-67 years old) with mild to moderate hemiparesis at acute stages and chronic stages at least 1 month later. Normal subjects (3 females and 2 males, 47-63 years old) were also included. Unilateral hand movement activated predominantly the contralateral primary sensorimotor cortex in the normal subjects and the stroke patients when they moved unaffected hand. Affected hand movements activated bilateral sensorimotor cortices early after stroke (< 25 days of stroke onset), whereas the activation pattern returned toward normal at later periods (> 35 days). The contralaterality index (0.34 +/- 0.12 in normal control) was reduced at early periods (0.00 +/- 0.03, p < 0.01) after stroke, and returned to normal (0.35 +/- 0.24) as motor function recovered. These findings suggest that a transient increase in motor activation in the ipsilateral intact hemisphere within 1 month may play an important role in the recovery from motor dysfunction after stroke.     

Therapeutic time window of post-ischemic mild hypothermia and the gene expression associated with the neuroprotection in rat focal cerebral ischemia

Hypothermia is the only neuroprotective therapy proven to be clinically effective. Identifying the molecules that play important roles in the efficacy of hypothermia, we developed a multi-channel computer-controlled system, in which the brain temperatures of freely moving rats were telemetrically monitored and maintained below 35 degrees C, and examined the time window necessary to exert its significant neuroprotective effects. Eight-week-old SD rats were subjected to a 2h middle cerebral artery occlusion (MCAO) with an intraluminal filament, and post-ischemic hypothermia was introduced at 0, 2, 4, or 6h after reperfusion until the rats were killed 2 days after MCAO. Since a significant protection was observed when hypothermia was started within 4h after reperfusion, it was concluded that the therapeutic time window of mild hypothermia lasts for 4h after reperfusion in our model. On the basis of the window, comprehensive gene expression analyses using oligonucleotide microarrays were conducted and identified potential genes related to the efficacy of hypothermia, which included inflammatory genes like osteopontin, early growth response-1, or macrophage inflammatory protein-3alpha. Therefore, the neuroprotective effects of post-ischemic mild hypothermia were strongly suggested to be mainly associated with the reduction of neuronal inflammation.     

Synaptic vesicle dynamics in the mossy fiber-CA3 presynaptic terminals of mouse hippocampus

The mossy fiber (MF)-CA3 synapse in the hippocampus is unique in the CNS because of its wide dynamic range of transmitter release during short- and long-term plasticity. The presynaptic mechanisms underlying the fidelity of transmission were investigated for the MF-CA3 synapses. The relative size of readily releasable pool (RRP) of vesicles was estimated by counting the number of docked vesicles at an active zone (AZ) on the transmission electron microscopy (TEM) image. The size of the releasable pool and the exo-endocytosis kinetics were directly measured from individual large MF boutons in hippocampal slices of transgenic mice that selectively express synaptopHluorin (SpH), a pH-sensitive GFP fused to the lumenal aspect of one of the vesicular membrane proteins, VAMP-2, in these boutons. Here we found (1) there are distinct two vesicle pools, the resting pool which is resistant to exocytosis, and the releasable pool, (2) the initially docked vesicles are easily depleted and the RRP is maintained by refilling from the reserve subpopulation of releasable pool ("reserve" releasable pool), and (3) the contribution of rapid reuse of recycled vesicles is relatively small. Therefore, the fidelity of transmission is suggested to be ensured by the rapid refilling rate of RRP.