Regional cerebral blood flow in a patient with Nasu-Hakola disease

We report a functional neuroimaging study of a 43-year-old woman with Nasu-Hakola disease (NHD). Regional cerebral blood flow (rCBF) images were measured with technetium-99m ethyl cysteinate dimer single photon emission computed tomography (SPECT). rCBF was decreased in the bilateral frontal lobes and thalamus. This finding was consistent with the known underlying neuropathology in patients with NHD. Brain SPECT is useful for demonstrating the pathophysiologic brain region in patients with NHD.     

Serous retinal detachment in an elderly patient with Philadelphia-chromosome-positive acute lymphoblastic leukemia

PURPOSE: To describe an elderly woman who presented with a serous retinal detachment (SRD) as the first sign of Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). DESIGN: Observational case report. METHODS: A complete ophthalmic and systemic evaluation was performed on a 62-year-old woman because of decreased vision of 20/60 OD and 20/25 OS. RESULTS: Fundus examination revealed a SRD involving the fovea, OU. Fluorescein angiography disclosed multifocal spots of hyperfluorescence in the early phase, and diffuse subretinal accumulation of fluorescein in the late phase. She was diagnosed with Ph(+) ALL because of systemic findings. She underwent systemic chemotherapy and went into complete remission. Visual acuity improved to 20/20 in both eyes with resolution of the bilateral SRD. CONCLUSIONS: Our observations indicate that a sudden appearance of SRD, even in an elderly patient, warrants a thorough systemic screening for underlying leukemia. This is especially important, because prompt systemic chemotherapy can improve the visual acuity and the prognosis.     

A new method for comprehensive bird's-eye analysis of the surgically excised internal limiting membrane

PURPOSE: To investigate the role of cells and extracellular matrix on the internal limiting membrane (ILM), we demonstrated a new method for a comprehensive bird's-eye analysis of surgically excised ILM. DESIGN: Laboratory investigation. METHODS: The ILM of an idiopathic epiretinal membrane was fixed and spread out onto a glass slide, using fine needles under a biomicroscope. The expanded ILM was analyzed by light microscopy, immunohistochemistry, and scanning electron microscopy. RESULTS: The excised ILM could be unfolded and spread out as a flat sheet onto the glass slide. Immunohistochemistry revealed that most migrating cells were glial cells. Scanning electronmicroscopy revealed that the vitreous surface of the ILM was smooth, in contrast to the rough retinal surface. The ILM showed abundant cellular migration as a continuous stratified cellular sheet. CONCLUSIONS: This new bird's-eye-view observation of excised ILM enables us to carry out comprehensive analysis of cellular distribution from a temporal and spatial perspective.     

Characterization and distribution of bone marrow-derived cells in mouse cornea

PURPOSE: Bone marrow (BM)-derived stem cells are thought to possess extensive differentiation capacity. The present study was conducted to investigate the characteristics and distribution of these cells in the normal mouse cornea. METHODS: BM cells and BM-derived hematopoietic stem/progenitor cells (HSCs) from enhanced GFP (eGFP) transgenic mice (lin(-), Sca-1(+)) were intravenously transplanted into irradiated wild-type C57BL/6 mice. At 4 to 6 months after transplantation, the mice were killed, and their whole corneas examined by histologic and immunohistochemical methods (CD11c, CD11b, and CD45). RESULTS: At 2 weeks after BM cell transplantation, GFP(+) cells gradually migrated into the cornea from the limbal area. At 2 to 6 months, they were distributed over the entire cornea. In cross sections of whole cornea, GFP(+) cells comprised 27.3% +/- 11.1% (BM) and 24.0% +/- 8.01% (HSC) of total cells in the peripheral corneal stroma. In the center of the corneal stroma, GFP(+) cells were 7.58% +/- 2.63% (BM) and 8.06% +/- 1.76% (HSC) of total cells. Immunohistochemistry showed that GFP(+) CD11c(+), CD11b(+), CD11c(-), and CD11b(-) cells occupied the entire corneal stroma. CONCLUSIONS: The present study provides direct evidence of the distribution of BM-derived cells in the mouse cornea. Immunohistochemical study showed that some of these cells are BM-derived antigen-presenting cells such as dendritic cells and macrophages. Some elements of BM-derived cells may continue to exist in the corneal stroma.     

Identification of key amino acids in the gastrin-releasing peptide receptor (GRPR) responsible for high affinity binding of gastrin-releasing peptide (GRP)

The bombesin (Bn) receptor family includes the gastrin-releasing peptide (GRPR) and neuromedin B (NMBR) receptors, Bn receptor subtype 3 (BRS-3) and Bn receptor subtype 4 (BB(4)). They share 50% homology, yet their affinities for gastrin-releasing peptide (GRP) differ. The determinants of GRP high affinity for GRPR and BB(4), and low affinity for BRS-3 are largely unknown. To address this question we made an analysis of structural homologies in Bn receptor members correlated with their affinities for GRP to develop criteria to identify amino acids important for GRP selectivity. Fourteen differences were identified and each was mutated singly in GRPR to that found in hBRS-3. Eleven mutants had a loss of GRP affinity. Furthermore, three of four amino acids in the GRPR selected used a similar approach and previously reported to be important for high affinity Bn binding, were important for GRP affinity. Some GRPR mutants containing combinations of these mutations had greater decreases in GRP affinity than any single mutation. Particularly important for GRP selectivity were K101, Q121, A198, P199, S293, R288, T297 in GRPR. These results were confirmed by making the reverse mutations in BRS-3 to make GRP gain of affinity mutants. Modeling studies demonstrated a number of the important amino acids had side-chains oriented inward and within 6A of the binding pocket. These results demonstrated this approach could identify amino acids needed for GRP affinity and complemented results from chimera/mutagenesis studies by identifying which differences in the extracellular domains of Bn receptors were important for GRP affinity.