Autopsy findings of meningitis associated with multiple brain infarctions in two adult patients

Cerebrovascular complications of meningitis have been extensively documented in the literature. It is little known, however, that paroxysmal, devastating, and potentially fatal complications can occur when the early signs of infection are subtle and missed. We describe the clinical course and neuropathological findings of the occurrence of brain infarctions during two atypical clinical courses of meningitis. In one patient, it was due to Serratia marcescens detected only by an autopsy specimen, and in the other, it was due to Aspergillus detected by a surgical biopsy. Death followed multiple, extensive, and progressively multiplicative infarctions in the basal ganglia, brainstem, and cerebral cortices. Autopsies revealed that the infarctions were caused by severe inflammatory change in the vascular walls, mainly of the arteries of the skull base, including the basilar and carotid arteries. Thrombus formation was also recognized in the lumen of several arteries. A number of characteristic Aspergillus hyphae were recognized in the arterial wall of one patient. Meningitis, which may be associated with severe vasculitis and lead to cerebral infarction, should be considered in the differential diagnosis of these conditions. Early diagnosis and initiation of vigorous therapy should be stressed for therapeutic success.     

Cytoskeleton and surface structures of cells directly attached to the tooth in the rat junctional epithelium

OBJECTIVE: It is still an open question whether cells directly attached to the tooth (DAT) cells are migratory or non-migratory cells. The purpose of this study was to examine cytoskeletal and surface structures of DAT cells that might be involved in migration. METHODS: We investigated the distribution of stress fibers composed of actin filaments in DAT cells using phallacidin fluorescent dye methods in a confocal laser scanning microscope. To observe the three-dimensional structure of the DAT cell surface, the osmium maceration scanning electron microscope (SEM) method, which removes various soluble materials between DAT cells and the enamel, was employed. RESULTS: Stress fibers were found in the most apically located DAT cells, and were arranged in parallel to the presumable cervical-line, whereas some of the fibers ran parallel to the tooth axis in the more coronally located DAT cells. The parallel arrangement to the tooth axis of the fibers may be involved with migration for turnover, and the parallel accumulation to the presumable cervical-line may be concerned with the cervical contraction of DAT cells. Osmium maceration SEM images at high magnification revealed the existence of microvilli-like structures on the enamel surfaces (facing to the tooth surface) of DAT cells after removal of the soluble matrices. The thicknesses of the microvilli-like structures on the enamel surfaces and cell processes of intercellular bridges were significantly different. CONCLUSION: DAT cells possess stress fibers arranged in parallel to the tooth axis and to the presumable cervical-line in the cytoplasm, and microvilli-like structures on their enamel surfaces. These results suggest that these structures contribute to DAT cell migration.     

Chronic food restriction enhances memory in mice--analysis with matched drive levels

We compared the effects of chronic and acute food deprivation on learning and memory using a dry-type water maze, active avoidance and passive avoidance in C57BL/6L mice. The drive level of the animals--under acute and chronic food deprivation--was matched by a progressive ratio schedule. Both deprivations led to a high degree of activity in the animals; however, the animals on an acute dietary restriction did not exhibit a significantly better performance than those on ad libitum feeding, while those on a chronic food deprivation exhibited memory enhancement. These effects were subtle and were found at a later stage of learning. These findings suggest that chronic food restriction induces memory consolidation or resistance to memory reduction in addition to increased activity.     

The NK1 receptor and its participation in the synergistic enhancement of corneal epithelial migration by substance P and insulin-like growth factor-1

1. We have previously shown that substance P (SP) and insulin-like growth factor-1 (IGF-1) act synergistically to enhance the migration of rabbit corneal epithelial cells in an organ culture model. The present study was designed to identify the epithelial cell SP receptor that participates in this synergistic effect.
2. Rabbit corneal blocks were incubated for 24 h, then the length of the path of epithelial migration was measured. Reagents tried in the TC-199 culture medium, in the presence or absence of IGF-1, were: SP, agonists of tachykinin receptors NK₁, NK₂ or NK₃ and antagonists of tachykinin receptors NK₁ or NK₂.
3. The binding characteristics of SP receptors were examined in rabbit cultured corneal epithelial cells by binding assays with [¹²⁵I]-SP in the presence or absence of excess unlabelled SP or ligands of NK₁, NK₂ or NK₃ receptors.
4. As was demonstrated previously, SP and IGF-1 stimulated epithelial migration when they were added to the culture medium together, but individually they had no effect. NK₁ agonists had the same synergistic effect with IGF-1 as did SP, but the NK₂ and NK₃ agonists did not. Furthermore, the NK₁ antagonist abolished the synergistic effect of SP and IGF-1, but the NK₂ antagonist had no effect.
5. SP bound specifically to rabbit cultured corneal epithelial cells. The binding affinity was 0.44 nM and there were 2.43×10⁴ binding sites per cell. The NK₁ ligand competed, in a dose-dependent fashion, with the binding of SP to corneal epithelial cells, but neither the NK₂ nor NK₃ ligand affected binding.
6. We conclude that the SP receptor in rabbit corneal epithelial cells is NK₁ and that this receptor participates in the synergistic enhancement of corneal epithelial migration by SP and IGF-1. The precise mechanism(s) of this interaction requires more study. These findings imply that both neural and humoral factors are essential for the maintenance and healing of corneal epithelium.

     

KHM-1, a novel plasmid-mediated metallo-beta-lactamase from a Citrobacter freundii clinical isolate

A novel gene, bla_KHM-1, encoding a metallo-β-lactamase, KHM-1, was cloned from a clinical isolate of Citrobacter freundii resistant to most β-lactam antibiotics. Escherichia coli expressing bla_KHM-1 was resistant to all broad-spectrum β-lactams except for monobactams and showed reduced susceptibility to carbapenems. Recombinant KHM-1 exhibited EDTA-inhibitable hydrolytic activity against most β-lactams, with an overall preference for cephalosporins.     

Cell-printing and transfer technology applications for bone defects in mice

Bone regeneration therapy based on the delivery of osteogenic factors and/or cells has received a lot of attention in recent years since the discovery of pluripotent stem cells. We reported previously that the implantation of capillary networks engineered ex vivo by the use of cell-printing technology could improve blood perfusion. Here, we developed a new substrate prepared by coating glass with polyethylene glycol (PEG) to create a non-adhesive surface and subsequent photo-lithography to finely tune the adhesive property for efficient cell transfer. We examined the cell-transfer efficiency onto amniotic membrane and bone regenerative efficiency in murine calvarial bone defect. Cell transfer of KUSA-A1 cells (murine osteoblasts) to amniotic membrane was performed for 1 h using the substrates. Cell transfer using the substrate facilitated cell engraftment onto the amniotic membrane compared to that by direct cell inoculation. KUSA-A1 cells transferred onto the amniotic membrane were applied to critical-sized calvarial bone defects in mice. Micro-computed tomography (micro-CT) analysis showed rapid and effective bone formation by the cell-equipped amniotic membrane. These results indicate that the cell-printing and transfer technology used to create the cell-equipped amniotic membrane was beneficial for the cell delivery system. Our findings support the development of a biologically stable and effective bone regeneration therapy.     

Protein kinase A activation down-regulates, whereas extracellular signal-regulated kinase activation up-regulates sigma-1 receptors in B-104 cells: Implication for neuroplasticity

The sigma-1 receptor (Sig-1R) can bind psychostimulants and was shown to be up-regulated in the brain of methamphetamine self-administering rats. Up-regulation of Sig-1Rs has been implicated in neuroplasticity. However, the mechanism(s) whereby Sig-1Rs are up-regulated by psychostimulants is unknown. Here, we employed a neuroblastoma cell line B-104, devoid of dopamine receptors and transporter, and examined the effects of psychostimulants as well as cAMP on the expression of Sig-1Rs in this cell line, with a specific goal to identify signal transduction pathway(s) that may regulate Sig-1R expression. Chronic treatments of B-104 cells with physiological concentrations of cocaine or methamphetamine failed to alter the expression of Sig-1Rs. N6,2'-O-Dibutyryl-cAMP (dB-cAMP), when used at 0.5 mM, caused a down-regulation of Sig-1Rs that could be blocked by a protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89). However, dB-cAMP, when used at 2 mM, caused an up-regulation of Sig-1Rs that was insensitive to the H-89 blockade but was partially blocked by an extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone). Furthermore, 2 mM dB-cAMP induced an ERK phosphorylation lasting at least 90 min, at which time the phosphorylation caused by 0.5 mM dB-cAMP had already diminished. PD98059, applied 90 min after addition of 2 mM dB-cAMP, attenuated the Sig-1R up-regulation. Our results indicate that cAMP is bimodal in regulating Sig-1R expression: a down-regulation via PKA and an up-regulation via ERK. Results also suggest that psychostimulants may manipulate the cAMP-PKA-Sig-1R and/or the cAMP-ERK-Sig-1R pathways to achieve a neuroplasticity that favors addictive behaviors.     

Long-term follow-up of atypical membranoproliferative glomerulonephritis: are steroids indicated?

Atypical membranoproliferative glomerulonephritis (MPGN) has been reported to have a good prognosis when treated with corticosteroids. However, this recommendation is based on uncontrolled trials and is associated with many complications. The purpose of our study is to determine whether steroid therapy is indicated for atypical MPGN. The cases of seven patients with atypical MPGN are reported in this study. Urinary abnormalities of five of them were detected by urine screening at school, of two because of macrohematuria. Hypocomplementemia was noted in six patients. All but one patient were treated without corticosteroids, and five with angiotensin-converting enzyme inhibitors (ACEI) and/or the Chinese herbal medicine Sairei-to (TJ-114). One patient recovered spontaneously from proteinuria and was therefore not treated, and one who developed severe proteinuria during observation was treated with corticosteroids. After an average follow-up period of 10.0 years, five patients showed normal urinary findings, one had hematuria and one proteinuria. At the most recent follow-up, the renal function of all patients remained within the normal range, and serum C3 had returned to normal levels in five out of six. These findings suggest that the indication of steroid therapy for atypical MPGN should be re-examined, since most of the patients with atypical MPGN seem to have an excellent prognosis without treatment with corticosteroids.