C-reactive protein levels are associated with cerebral small vessel-related lesions.

OBJECTIVE: Inflammation has received increasing attention as a cause of stroke. Although several lines of evidence suggest that inflammatory processes have a role in arteriosclerotic vascular events, their involvement remains to be determined. The purpose of this study was to examine the associations between serum high-sensitive C-reactive protein (hs-CRP) levels and cerebral small vessel (CSV)-related lesions as a manifestation of arteriosclerosis. MATERIALS AND METHODS: Neurologically normal subjects without any history of neurologic or psychiatric diseases were enrolled (n = 519). All the participants underwent magnetic resonance imaging (MRI), and their CSV-related lesions (i.e., lacunar infarcts, cerebral microbleeds, deep white matter hyperintensity, and periventricular hyperintensity) were evaluated. The serum levels of hs-CRP were evaluated as common inflammatory markers. RESULTS: Subjects with higher C-reactive protein (CRP) levels had more lacunar infarcts (P = 0.02). After adjusting for the traditional cardiovascular risk factors, higher hs-CRP levels were still associated with the presence of lacunar infarcts [odds ratio for the highest vs the lowest tertile of hs-CRP, 3.57 (95% confidence interval: 1.30-9.80)]. These associations did not change when the logarithmically transformed values for hs-CRP were included. Furthermore, subjects with higher CRP levels had more cerebral microbleeds (P = 0.03), more severe deep white matter hyperintensity (P = 0.04), and periventricular hyperintensity (P = 0.04); however, these associations were not observed after adjusting for the cardiovascular risk factors. CONCLUSIONS: Higher levels of hs-CRP were associated with lacunar infarcts. Thus, inflammatory processes may be involved in the pathogenesis of small-vessel disease.

Magnetic stimulation and movement-related cortical activity for acute stroke with hemiparesis.

BACKGROUND AND PURPOSE: This double-blind, randomized, placebo-controlled study investigated the beneficial effects of repetitive transcranial magnetic stimulation (rTMS) to patients with motor paresis in acute subcortical stroke on functional recovery and electrophysiological measures. METHODS: Twenty patients with acute stroke were randomized into real rTMS (n = 10) or sham (n = 10) groups. Patients received five daily sessions of rTMS with 1200 pulses at 1 Hz for 20 min or sham stimulation over the contralesional motor cortex. Movement-related cortical potential MRCP, consisting of the Bereitschaftpotential, negative slope (NS') and motor potential (MP), was recorded during self-paced wrist extension of the affected limb associated with assessment of the Fugl-Meyer assessment (FMA) of the upper extremity, the pegboard test and the grip strength before and after the rTMS session. RESULTS: Real rTMS improved the FMA and pegboard test scores compared to the sham group in the affected hand. This improvement was associated with increases in the MP and NS' over the front-central sites in the ipsilesional hemisphere, whereas the sham group did not show significant changes in MRCP components by rTMS. CONCLUSIONS: Our findings suggest that low-frequency rTMS to the contralesional motor cortex facilitates functional recovery of paretic limbs in acute stroke patients through enhancing the the neuronal activity of ipsilesional motor and pre-motor areas.

Polycomb gene product Bmi-1 regulates stem cell self-renewal.

The Polycomb group (PcG) gene Bmi-1 has recently been implicated in the maintenance of hematopoietic stem cells (HSCs). However, the role of each component of PcG complex in HSCs and the impact of forced expression of PcG genes on stem cell self-renewal remain to be elucidated. To address these issues, we performed both loss-of-function and gain-of-function analysis on various PcG proteins. Expression analysis revealed that not only Bmi-1 but also other PcG genes are predominantly expressed in HSCs. Loss-of-function analyses, however, demonstrated that absence of Bmi-1 is preferentially linked with a profound defect in HSC self-renewal, indicating a central role for Bmi-1, but not the other components, in the maintenance of HSC self-renewal. Over-expression analysis of PcG genes also confirmed an important role of Bmi-1 in HSC self-renewal. Our findings indicate that the expression level of Bmi-1 is the critical determinant for the self-renewal capacity of HSCs. These findings uncover novel aspects of stem cell regulation exerted through epigenetic modifications by the PcG proteins.

A case-control study of lung cancer with special reference to asbestos exposure.

A case-control study of lung cancer was carried out in Yokosuka City, Kanagawa Prefecture, the location of a pre-war Japanese Imperial naval factory and present site of a U.S. naval base. Cytologically or pathologically confirmed male fatal cases of lung cancer during the period of 1978 to 1982 in Yokosuka Kyosai Hospital were compared with a control group in the same hospital. Controls who died from causes other than cancer, pneumoconiosis, accident, or suicide were matched by age to the cases. Information that included occupational and smoking history was obtained by interviews with the families of the 96 cases and 86 controls. Major results were as follows: a) The relative risks of lung cancer associated with asbestos exposure and suspected exposure were 2.41 (p less than 0.05) and 1.56, respectively, after controlling for age and smoking history, and the relative risk associated with smoking was 6.01 (p less than 0.05) after adjusting for age and asbestos exposure. b) The age- and smoking-adjusted relative risks of lung cancer associated with asbestos exposure were 3.40 (p less than 0.01) and 1.72 for Kreyberg groups I and II, respectively. Significantly elevated relative risk associated with smoking history was demonstrated for Kreyberg group I, but not for group II, after controlling for age and asbestos exposure.

Medication-induced hallucination and cerebral blood flow in Parkinson's disease.

Although hallucinations in Parkinson's disease (PD) are not unusual in the long-term treatment with anti-parkinsonian agents, their mechanism is not fully understood. We compared both the neuropsychiatric state and the results of 99mTc-labeled hexamethyl propyleneamine oxime single-photon emission computed tomography in 12 PD patients with medication-induced hallucinations and 21 PD patients without hallucinations. Hallucinatory patients showed significantly lower cerebral blood flow in left temporal regions than nonhallucinatory patients. The cerebral blood flow reduction in these regions may be related to the mechanism of medication-induced hallucinations in PD.

[Physiological roles of rhodopsin phosphorylation and dephosphorylation and its relationship with retinitis pigmentosa].

Light signals are converted into electrical signals by vertebrate photoreceptor cells, and the generated electrical signals are then modulated within retinal neurons and brain. During the visual transduction precesses in the photoreceptor cells, there are basically three functions. That is, (1) photoexcitation, (2) quenching of the photoexcitation, and (3) adaptation. These functions are precisely regulated by enzymatic cascade reactions. Quite recently, it was shown that rhodopsin phosphorylation occurred at different sites with different kinetics, in vivo, and this may be a control mechanism for both quenching and adaptation. Furthermore, autosmal retinitis pigmentosa (RP) with rhodopsin mutation at 296 Lys, which in the binding site of 11-cis-retinal, showed constitutive activation of guanosine 5'-triphosphate (GTP) binding protein and no rhodopsin phosphorylation by rhodopsin kinase. These observations suggest that rhodopsin phosphorylation and dephosphorylation are critical for understanding visual transduction and pathophysiology of RP.

[A case of abducens nerve palsy after whiplash injury].

We report a patient who developed abducens nerve palsy after whiplash injury. The patient was a 61-year-old man who was involved in a traffic accident on May 15, 1993. After the accident, he developed severe neck pain. Four days later, he still had neck pain and vertigo. On the fifth day after the accident, he noted diplopia on left gaze and visited our hospital. Neurologic examination revealed an isolated abduction deficit of the left eye. Head magnetic resonance imaging and angiography showed no abnormal findings. Ten days later, the ocular movements of the patient were full and the diplopia disappeared. About two months later, his neck pain and vertigo also resolved. In this patient, the abducens nerve palsy was caused by whiplash injury and was in full recovery.

[A six year follow-up study on the influence of silent ischemic brain lesions on cognitive function and brain atrophy in elderly people].

METHODS: To investigate the influence of silent ischemic brain lesions (silent brain infarction (SBI) and periventricular hyperintensity (PVH) on cognitive function and brain atrophy, we studied MRI and cognitive tests in 27 healthy elderly people (above 65 years old) for 6 years. We examined Okabe's Scale for verbal intelligence, Koh's Block Design Test for performance intelligence and Zung's Self-rating Depression Scale (SDS). On MRI, lesions with high intensity on T2-weighted image and low intensity on T1-weighted image, and which were larger than 3 mm were diagnosed as SBI. The PVH was classified into 5 grades (0-4), and we divided the subjects into the PVH 0-1 group and the PVH 2-4 group. We evaluated brain atrophy using the ventricular area index (VAI) (the ratio of ventricular area to intracranial area at the level of lateral ventricle) on MRI by NIH image 1.55 (Macintosh). RESULTS: The SBI group and the PVH 2-4 group showed significant decline in Okabe's Score, and Koh's IQ, increase in SDS and VAI during six years. On the other hand, the non-SBI and the PVH 0-1 group showed a decline only in Okabe's score, and an increase in VAI. The rate of change in VAI was significantly higher in the subjects with SBI than those without it. However, there was no significant difference in the VAI change rate between the PVH 2-4 group and the PVH 0-1 group. CONCLUSION: Silent ischemic brain lesions such as SBI and PVH may have significant influence on decline of cognitive functions and progression of brain atrophy even in healthy elderly people.

Bmi1 is essential for leukemic reprogramming of myeloid progenitor cells.

The polycomb group (PcG) proteins, particularly Bmi1, have an essential role in maintaining the self-renewing capacity of leukemic stem cells (LSCs). Although one of their major targets in LSCs is known to be the Ink4a/Arf tumor suppressor gene locus, the role of PcG proteins in the leukemic reprogramming of target cells into LSCs is not well characterized. In this study, Bmi1(-/-) granulocyte/macrophage progenitors (GMPs) were transformed with the leukemic fusion gene MLL-AF9. Although Bmi1 was not essential to the immortalization of GMPs in vitro, Bmi1(-/-) cells showed enhanced differentiation and retained less LSCs. A number of genes were derepressed in the absence of Bmi1 including potential tumor suppressor genes. Transplantation assays demonstrated that Bmi1 was indispensable for the development of leukemia in vivo and deletion of both the Ink4a and Arf genes only partially restored the leukemogenic capacity of Bmi1(-/-) LSCs. Of note, the complementation of immortalized Bmi1(-/-)Ink4a-Arf(-/-) GMPs with Bmi1 failed to restore the expression of the majority of deregulated genes and leukemogenic activity in vivo. These findings indicate that Bmi1 is essential for the faithful reprogramming of myeloid progenitors into LSCs and unveil that leukemic fusion genes require PcG proteins exerting an effect in concert to establish LSC-specific transcriptional profiles, which confer full leukemogenic activity on LSCs.

Sex differences in morphology of the brain stem and cerebellum with normal ageing.

The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the cerebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women.