PubMed HealthSearch

Biomedical subjects

J Kimura

Publications and source records attributed to J Kimura.

At least 19 recordsLinked to original sources

Regional accumulation of amyloid beta/A4 protein precursor in the gerbil brain following transient cerebral ischemia.

Alterations of beta/A4 amyloid protein precursor (APP) were investigated immunohistochemically in the gerbil brain after transient global ischemia and subsequent reperfusion. Marked accumulation of this protein peaking at 24 h occurred in the neurons of the CA3 and paramedian region of the hippocampus as well as layers III, V and VI of the cerebral cortex. On the contrary, the accumulation was not observed in the neurons of the CA1 region. These results indicate that distribution of APP is altered depending on tissue viabilities after cerebral ischemia.

Amyloid beta-Protein Precursor

Soybean agglutinin binds commonly to a subpopulation of small-diameter neurons in dorsal root ganglion, vascular endothelium and microglia in human spinal cord.

Soybean agglutinin (SBA) was used to identify the location of N-acetylgalactosaminyl glycoconjugates in human dorsal root ganglia (DRG) and spinal cord. SBA bound to a subpopulation of small-diameter neurons in DRG and their central projections. It also bound to microglia and vascular endothelium. Vascular endothelium, DRG neurons and microglia do not originate from the neural tube, but penetrate into the neural tube in the embryonic stage and thereafter are located in the spinal cord. SBA binding glycoconjugates may be responsible for cell-cell interaction between these three cell types and tissues in human spinal cord.

Acetylglucosamine

Topographic projections from the subiculum to the limbic regions of the medial frontal cortex in the cat.

When WGA-HRP was injected into the subicular cortex of the ventral hippocampal formation (Hv) in the cat, terminal labeling was seen ipsilaterally in the caudoventral parts of the medial frontal cortex: in the infralimbic cortex (area 25), ventral part of the prelimbic cortex (area 32), and caudoventral part of the orbitofrontal cortex (area 12). The terminal labeling was observed in all cortical layers except layer 1. The cells of origin of these projections were then confirmed to be pyramidal neurons in the subiculum of the Hv. The projections were topographically organized: the temporal-septal shift along the long axis of the subiculum of the Hv corresponded to a rostroventral-caudodorsal shift in the anterogradely labeled limbic regions of the medial frontal cortex.

Animals

Phosphatidylinositol-specific phospholipase C activity in the postmortem human brain: no alteration in Alzheimer's disease.

The activity of phospholipase C (PLC) which hydrolyzes exogenous phosphatidylinositol (PI), was investigated in samples prepared from postmortem normal human brains and Alzheimer disease brains. The enzyme activity did not change significantly after rat brains were left for 24 h at room temperature. The PI-specific PLC activity in the Alzheimer cytosolic and particulate fractions was not significantly different from that in the control fractions. The PI-specific PLC activity as a function of the free Ca2+ concentration was also similar between control and Alzheimer brains. These results suggest that the PI-specific PLC activity is not altered in Alzheimer's disease.

Aged

Localization of protein kinase C in human skeletal muscle.

The immunolocalization of protein kinase C (PKC) isozymes alpha, beta I and beta II, was investigated in human skeletal muscle. All three isozymes were present on the muscle fiber surface membrane and within the muscle fibers. The alpha-isozyme was most clearly delineated on the surface membrane of the muscle fiber and on small blood vessels in the connective tissue. The axons of myelinated intramuscular nerves stained intensely for the beta I isozyme, whereas the endoneurial connective tissue reacted more strongly for the alpha- and beta II-isozymes. PKC isozymes may regulate intracellular signal transduction in human skeletal muscle, as in the other tissues, but their exact role in muscle remains unknown.

Adult

Occurrence of acetylcholinesterase activity closely associated with amyloid beta/A4 protein is not correlated with acetylcholinesterase-positive fiber density in amygdala of Alzheimer's disease.

To investigate the possible relationship between acetylcholinesterase (AChE)-containing fiber density and senile plaque density and between AChE-positive plaques and beta/A4 protein deposition, AChE histochemistry, the modified Bielschowsky's method and beta/A4 protein immunohistochemistry were performed on the amygdala of Alzheimer's disease (AD) and aged control cases. Abundant AChE-positive senile plaques were found in the amygdala and related structures in AD. These AChE-positive plaques were mainly of the primitive or diffuse type. In addition to senile plaques of typical morphologies a variety of AChE-positive structures were observed in the amygdala and related regions in AD. A comparison of serial sections stained alternatively with AChE histochemistry and beta/A4 protein immunohistochemistry has revealed that these AChE-positive structures with variable morphological appearances displayed beta/A4 protein immunoreactivity, indicating that AChE is localized in a variety of beta/A4 protein deposition including the diffuse plaque. Thus, it is suggested that AChE is present in some senile plaques at the earliest stage. However, there was no apparent correlation between the numerical density of AChE-positive fibers and senile plaque density. These findings suggest that the degeneration of cholinergic neurons is not attributed to the occurrence of AChE activity in beta/A4 protein.

Acetylcholinesterase

Immunohistochemical localization of the proteinase inhibitor region of amyloid precursor proteins in the neocortex of Alzheimer's disease and aged controls.

The immunohistochemical localization of the proteinase inhibitor region of amyloid protein precursors (APPI) in the postmortem human neocortex was studied using a polyclonal antibody raised against a purified recombinant human APPI derivative produced by COS-1 cells. APPI-like immunoreactivity (APPI-LI) was found diffusely in the human neocortex. APPI-LI appeared as irregularly shaped granular structures. The size of the APPI-LI structures was 1-4 microns in diameter. APPI-LI usually formed a cluster of 10- to 20-microns diameter in the cortical gray matter and 20- to 40-microns diameter in the subcortical white matter. Double staining for APPI and glial fibrillary acidic protein indicated that APPI-LI in the white matter and molecular layer was localized exclusively in the fibrillary astrocytes. In contrast, APPI-LI was found in neurons as well as in the fibrillary astrocytes in layers II through to VI. Under fluorescence microscopy, APPI-LI in both neurons and fibrillary astrocytes were found in close association with lipofuscin. The present observations indicate that APPI is localized in neurons and astrocytes in the human neocortex and that APPI may be associated with lipofuscin or lysosome in the human neocortex.

Aged

Age-related changes in the proportion of amyloid precursor protein mRNAs in Alzheimer's disease and other neurological disorders.

In the human brain, alternative splicing of amyloid precursor protein (APP) gene transcript generates at least three types of mRNA coding for APP770, APP751 and APP695. The former two types harbor, but the latter one lacks a domain of Kunitz-type serine protease inhibitor (KPI). We studied, by using the RNase protection technique, the expression of APP mRNAs in brains of Alzheimer's disease (AD) and other neurological disorders with special reference to aging. We found that the ratio of (APP770 mRNA+APP751 mRNA)/APP695 mRNA in the frontal cortex increased approximately 1.5-fold in AD compared with other neurodegenerative or cerebrovascular disorders. The ratio in other neurological disorders did not change significantly from control even in their affected brain regions. On the other hand, we found a positive correlation between the ratio and age; the ratio (y) increased gradually with the advance of age (x) as expressed by y = 0.005x + 0.014 (r = 0.372) for the AD group, and y = 0.004x -0.037 (r = 0.486) for the non-AD group. These correlations indicate that the AD brain reached the same ratio of KPI-harboring to lacking APP mRNAs a few decades earlier than the non-AD brain in senescence. This finding of AD-specific and age-related change led us to the idea that a relative increase in KPI-harboring APPs over a KPI-lacking APP may perturb normal degradation of APPs, thereby leading to deposition of beta A4 protein as amyloid.

Aging

Accelerated rejection of allografted rat liver perfused with anti-ICAM-1 monoclonal antibody.

Infusion of mouse anti-rat ICAM-1 into the portal vein of ACI rat liver graft before transplantation resulted in accelerated rejection by LEW recipients (2.9 +/- 2.5 days), when compared to the ACI liver grafts perfused with either Lactate-Ringer's solution (9.8 +/- 1.3) or anti-human ICAM-1 mAb (9.8 +/- 3.1). Histologic features of anti-rat ICAM-1 perfused grafts were spotty ischemic necrosis, whereas those of control grafts were marked cellular infiltration. These combined survival and histologic data suggest that the accelerated rejection may be mediated by vascular deterioration.

Animals

Magnetic coil stimulation of the spinal cord in the dog. Effect of removal of bony structure on eddy current.

Magnetic coil stimulation applied to the spine excites the lumbosacral roots rather than the spinal cord itself. To evaluate the mechanism responsible for this phenomenon, the effects of volume conduction on the activation of neural elements were studied. In ten intact dogs compound muscle action potentials could be recorded in the soleus muscle only when the magnetic coil was placed over the cauda equina. After laminectomy and pediculotomy, compound muscle action potentials also could be elicited when the magnetic coil was placed over the spinal cord. These findings suggest that the bony structure surrounding the spinal cord interferes with the spread of magnetically induced eddy currents to the spinal cord.

Action Potentials

Suction effusion fluid from skin and constituent analysis: new candidate for interstitial fluid.

The authors analyzed the constituents of effuse transcutaneous fluid, labeled suction effusion fluid (SEF), and monitored its glucose concentration during glucose loading in rabbits (Japan White, female) under pentobarbital anesthesia. The SEF was sampled by suctioning corneal layer-stripped skin at 400 mmHg absolute pressure. The SEF proved to have nearly the same concentrations as serum for lower-molecular-weight substances such as glucose, creatinine, and urea nitrogens, but not for higher-molecular-weight substances such as serum proteins. The SEF protein concentration was one-fourth that of serum protein. Proteins > 100 kDa molecular mass were barely detectable in the SEF. Monitoring of SEF glucose change every 10 min during intravenous glucose loading was successfully accomplished, and SEF glucose concentration followed blood glucose concentration with a 10-min delay. The SEF was thought to consist of interstitial fluid and/or effuse fluid from small vessels in subcutaneous tissue.

Animals

Cheiro-oral-pedal syndrome.

The cheiro-oral syndrome is a well-known peculiar sensory disturbance seen around the corner of the mouth and in the palm of the hand on the same side. However, sensory disturbance around the corner of the mouth, in the palm of the hand and in the foot on the same side (cheiro-oral-pedal syndrome) has not been reported until now. We examined 2 cases of cheiro-oral-pedal syndrome; the lesion responsible was confirmed by magnetic resonance imaging to be in the medial lemniscus and in the ventral ascending tract of the trigeminal nerve.

Aged

Sphenoid sinus mucocele with recurrent visual disturbance.

We present a case of sphenoid sinus mucocele with recurrent visual disturbance on the same side. A 22-year-old female showed two episodes of visual disturbance in the left eye for 3 months, and acute retrobulbar optic neuritis was diagnosed. With corticosteroid, visual disturbance improved in 1 week. MRI and CT scans showed mucocele in the left sphenoid sinus, and left optic nerve swelling with high intensity was observed in T2-weighted MRI. No destruction of the optic canal was found. The contiguous inflammation in the optic nerve rather than compression was considered as pathogenesis.

Adult

Significance of low perfusion with increased oxygen extraction fraction in a case of internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Decreased cerebral blood flow with an increased oxygen extraction fraction, the so-called misery perfusion syndrome, suggests a vulnerability to reduction in cerebral perfusion pressure and a tendency to develop cerebral infarction. It is uncertain, however, whether the infarct would occur in the brain region specifically exhibiting this condition. CASE DESCRIPTION: We report the case of a patient with right intracranial internal carotid artery stenosis who presented with mild left hemiparesis resulting from a right frontal watershed infarct. Positron emission tomography 2 months after the stroke showed decreased cerebral blood flow with an increased oxygen extraction fraction in noninfarcted areas of the affected hemisphere. Maximal changes were detected in the watershed area between the middle cerebral artery and the posterior cerebral artery. Three months later, while on antiplatelet therapy, he suffered a new infarct in the right temporo-occipital watershed area that had shown the highest oxygen extraction fraction value on the first positron emission tomographic study. One month after the recurrence of stroke, a second study showed that low perfusion with increased oxygen extraction fraction persisted in the affected hemisphere to a lesser degree than in the first study. CONCLUSIONS: This observation suggests that the area of low perfusion exhibiting the highest oxygen extraction fraction has the highest risk for infarction. Increased oxygen extraction fraction may be an important factor in the development of hemodynamic infarction.

Brain

Hemodynamic and metabolic changes in crossed cerebellar hypoperfusion.

BACKGROUND AND PURPOSE: The pathophysiology of crossed cerebellar diaschisis remains to be elucidated. The mechanism responsible appears to be deafferentation through the corticopontocerebellar tract, which terminates in the cerebellar gray matter. However, few studies have demonstrated the hemodynamic and metabolic changes in the cerebellar gray matter and pons in crossed cerebellar diaschisis. METHODS: Using positron emission tomography in 24 patients with unilateral supratentorial stroke, we evaluated regional blood flow, metabolic rate of oxygen, oxygen extraction fraction, and blood volume in the cerebellar cortex and pons. Sixteen patients with significant cerebellar blood flow asymmetry, defined as a percentage difference in blood flow beyond the upper 95% confidence limit defined in eight normal subjects, were selected as the group with crossed cerebellar hypoperfusion. RESULTS: In patients with crossed cerebellar hypoperfusion, the metabolic rate of oxygen was significantly decreased in the cerebellar cortex contralateral to the supratentorial stroke, compared with that in the ipsilateral cerebellar cortex; this decrease was less than the decrease in cerebellar blood flow. The degrees of cerebellar asymmetry in these two parameters were negatively correlated with the metabolic rate of oxygen in the pons. The oxygen extraction fraction was slightly, but significantly, increased. In contrast to the ischemic state, however, the cerebellar blood volume was decreased, with no difference in the ratio of cerebellar blood flow to blood volume. CONCLUSIONS: These findings support interruption of the corticopontocerebellar tract as the mechanism of crossed cerebellar hypoperfusion. Our results also suggest a mild elevation in the oxygen extraction fraction in this state, with a mechanism distinct from ischemia.

Adult

Multifocal demyelinating motor neuropathy: cranial nerve involvement and immunoglobulin therapy.

We report two patients with multifocal demyelinating motor neuropathy whose symptoms improved after immunoglobulin infusion. Clinical signs included atrophy of the tongue and limb muscles, closely resembling that of motor neuron disease. Nerve conduction studies revealed multiple sites of motor conduction block without sensory abnormalities, suggesting selective involvement of motor fibers. Careful documentation of conduction block is required to diagnose this entity, which may be treated with immunoglobulin therapy.

Action Potentials