Paramedian thalamic and midbrain infarcts associated with palilalia

A patient with paramedian thalamic and midbrain infarcts developed palilalia.     

The map kinase ERK regulates renal activity of cyclin-dependent kinase 2 in experimental glomerulonephritis.

BACKGROUND: In vitro, the extracellular signal-regulated kinase (ERK) is an intracellular convergence point of multiple stimuli, which affect the cell cycle. However, the role of ERK in cell cycle regulation in vivo is unknown. METHODS: To address this issue, ERK activity was blocked both in vitro in mesangial cells (MC) and in vivo in experimental glomerulonephritis (GN) by a pharmacological inhibitor (U0126) of the ERK-activating kinase. RESULTS: In stimulated MC, inhibition of ERK reduced cyclin-dependent kinase 2 (CDK2) phosphorylation, CDK2 activity and cyclin E/A expression, whereas downregulation of CDK inhibitor p27(Kip1) expression was inhibited. In vivo, U0126 was given to rats in the acute phase of anti-Thy 1.1 GN. We previously showed that glomerular cell proliferation was reduced by 67% upon treatment with the inhibitor compared to nephritic controls. Now, we detected a significant increase in renal CDK2-activity/phosphorylation in the nephritic controls, that was significantly and dose-dependently reduced by ERK inhibition. CDK2 activation was accompanied by an increase in renal expression of cyclins E/A and the enhanced binding of these cyclins to CDK2 in the nephritic controls. These changes were blunted by U0126 treatment. Finally, we noted an increased expression and CDK2-binding of p27(KIP1) protein in the nephritic controls which was decreased in U0126 treated rats. CONCLUSIONS: Our observations provide the first evidence that ERK is an intracellular regulator of renal CDK2 activity in vivo in a glomerulonephritis model.     

Association of AKT1 with schizophrenia confirmed in a Japanese population.

BACKGROUND: Abnormality of the V-akt murine thymoma viral oncogene homologue 1 (AKT1) may be a predisposing factor in schizophrenia. Recent evidence supporting this hypothesis showed decreased AKT1 protein levels in patients with schizophrenia and significant association of AKT1 haplotypes according to the transmission disequilibrium test. METHODS: We provide the first replication of this evidence using a relatively large case-control sample (507 Japanese schizophrenia and 437 control subjects). We genotyped five single nucleotide polymorphisms (SNPs) from the original study and one additional SNP. RESULTS: We found a positive association with an SNP (SNP5) different from the original study's findings (SNP3) and also significance in the haplotypes constructed from the combination of SNP5. Linkage disequilibrium around SNP5 was complex and may produce this positive association. CONCLUSIONS: Our study provides support for the theory that AKT1 is a susceptibility gene for Japanese schizophrenia. Fine linkage disequilibrium mapping is required for a conclusive result.     

Increased alveolar fluid clearance following thoracotomy: Report of a case and results of an analysis

Alveolar fluid clearance was studied in the resected lung of a 58-year-old man who had undergone exploratory thoracotomy 9 days earlier. An isosmolar albumin solution was instilled into the distal air spaces, and the albumin and electrolyte concentrations were measured over 4h. Alveolar sodium and fluid clearance had increased by nearly 200% from the control values in the resected lungs of patients without prior thoracotomy (n=5), and histological examination showed that the number of alveolar type II epithelial cells was markedly elevated. These results suggest that an increase in the number of alveolar type II cells may accelerate alveolar fluid clearance under certain clinical conditions.     

Efficacy of prostaglandin I2 analog on liver grafts subjected to 30 minutes of warm ischemia

Due to the fact that no effective conditioning agent for hemodynamically unstable donors exists, the number of suitable donors is limited. The efficacy of OP-41483, a stable analog of prostaglandin I₂, as a conditioning agent of the liver was investigated in this study using pigs. OP-41483 was administered via the portal tributary for 10 min before 30 min of warm ischemia. Graft livers were procured after perfusion with OP-41483 in cold normal saline, the flushed with OP-41483 in Euro-Collins solution and placed in cold storage prior to orthotopic transplantation. OP-41483 was also administered intraportally for 120 min after reperfusion. Biochemical and histological studies, and survival rates were compared with a control group not given OP-41483 in an otherwise similar experimental protocol. The graft function recovered better in the OP group than in the control group, shown by the lactate values and lactate-to-pyruvate ratios. The marked congestion noted in the parenchyma of the control group livers was minimal in the OP group, verifying the microcirculatory effect of prostaglandin I₂ by its vasodilatory and antithrombotic actions. These findings suggest that OP-41483 has some protective effect as a conditioning agent in liver transplantation, with timing of administration being crucial.     

Spatial and temporal expression of fibril-forming minor collagen genes (types V and XI) during fracture healing

Skeletal development involves the coordinated participation of several types of collagen, including both major and minor fibrillar collagens. Although much is known about the major fibrillar collagens, such as types I and II, less is known about the minor fibrillar collagens, and their role in the repair and regeneration of bone has not been extensively studied. To clarify the role of minor fibrillar collagens in Fracture repair, we examined the spatial and temporal expression of mRNAs for pro-α2(V) collagen and pro-α1(XI) collagen in healing fractures in the rat by in situ hybridization and compared their patterns of expression with those Of mRNAs for pro-α1(I) collagen, pro-α1(II) collagen, and osteocalcin. A strong signal for pro-α2(V) was detected in the periosteal osteoprogenitor cells, whereas osteocalcin mRNA was strongly expressed only in the deep layers of the hard callus. The distribution of the pro-α2(V) signal was correlated with that of pro-α1(I) but was mutually exclusive of that of pro-α1(II).The expression of pro-α1(Xl) mRNA was synchronously regulated with that of pro-α1(II) during chondrogenesis in the soft callus. In the hard callus, pro-α1(XI) signal Was found in osteoblastic cells at the site of intramembranous and endochondral ossification. These cells simultaneously expressed pro-α2(V), although they were negative for pro-α1(II). These findings suggest that the, α2(V) collagen chain participates in the formation of the noncartilaginous fibrillar network in the hard callus and preferentially contributes to the initial stage of the intramembranous bone formation. Recent reports have, revealed that type-XI collagen, which had been classified as a cartilage-type collagen, is not necessarily specific for cartilage. The present results advanced this recognition and demonstrated a coexpression of α1(XI) mRNA and α2(V) mRNA in the noncartilaginous tissues in the fracture callus; this suggests the presence of tissue-specific and stage-specific heterotrimers consisting of α1(XI) and α2(V) collagen chains and the association of such hybrid trimers with the major fibrillar collagens in the process of fracture healing.     

Differential distribution of cellular forms of β-amyloid precursor protein in murine glial cell cultures

The production and localization of cell-associated forms of β-amyloid precursor protein (APP) of Alzheimer's disease was investigated in primary cultures of mouse glial cells. In both oligodendrocytes and astrocytes, immunofluorescence staining with an antibody against the car☐y terminus of APP revealed an intense cytoplasmic immunoreactivity. Immunoblotting of the cell extracts detected differences in the composition of APP between oligodendrocytes and astrocytes, notably the abundance of 107 kDa subtype in oligodendrocytes. Differences in immunoblot patterns were also noted between two buffer-insoluble, membrane-rich subcellular fractions of the glial cells, nuclear-mitochondrial and microsomal; the 119 kDa APP was enriched in the former, whereas the 73 and 115 kDa APPs in the latter. The results suggest that each APP subspecies may play a distinct functional role in different cell types and subcellular fractions.     

Cerebellar infarction restricted to bilateral inferior vermis presenting with floating sensation and then astasia]

A 76-year-old man suddenly experienced floating sensation, transient vertigo, and nausea. Neurological examination was unremarkable except for hypotonia and mild ataxia in the limbs, but orthostatic nausea and vomiting forced him to take a quiet, recumbent position. Magnetic resonance imaging of the brain showed cerebellar infarction restricted to the bilateral inferior vermis. During a course of recovery, he fell down in any directions while standing unattended. He was unable to keep the center of gravity on the feet base in an upright posture. The inferior vermis may participate in maintaining the center of gravity while standing.