Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord

In the developing spinal cord, signals from the roof plate are required for the development of three classes of dorsal interneuron: D1, D2, and D3, listed from dorsal to ventral. Here, we demonstrate that absence of Wnt1 and Wnt3a, normally expressed in the roof plate, leads to diminished development of D1 and D2 neurons and a compensatory increase in D3 neuron populations. This occurs without significantly altered expression of BMP and related genes in the roof plate. Moreover, Wnt3a protein induces expression of D1 and D2 markers in the isolated medial region of the chick neural plate, and Noggin does not interfere with this induction. Thus, Wnt signaling plays a critical role in the specification of cell types for dorsal interneurons.     

Ischemic "cross" tolerance in hypoxic ischemia of immature rat brain

The phenomenon of ischemic tolerance has been closely associated with the expression of heat shock proteins but recently, stress tolerance not related to hsp72 has been reported. In the present study, we focused on ischemic tolerance induced by hypoxia and hyperthermia in neonatal rat brain and analyzed the expression of hsp72. In a neonatal rat model of hypoxic ischemia (H-I), preconditioning by whole-body hyperthermia or hypoxia was induced 24 h prior to the ischemia. Brain damage was histologically evaluated and the expressions of hsp72 were analyzed. Hyperthermic preconditioning at 41 degrees C for 15 min, as well as hypoxic preconditioning with 8% hypoxia for 3 h, had almost complete neuroprotective effects. However, we failed to detect the expression of hsp72 in any of preconditioning. Only the H-I insult itself induced hsp72 in the dorsal striatum and slightly in the thalamus and the hippocampus. Hyperthermic preconditioning has neuroprotective effects which are comparable to hypoxic preconditioning in immature brain. The expression of hsp72 is not likely necessary for the ischemic tolerance in immature brain.     

Magnetic resonance imaging and histologic evidence of postoperative back muscle injury in rats

STUDY DESIGN: Postoperative back muscle injury was evaluated in rats by magnetic resonance imaging and histologic analyses. OBJECTIVE: To compare the magnetic resonance imaging manifestation of back muscle injury with the histologic findings in rats and to subsequently clarify the histopathologic appearance of the high intensity regions on T2-weighted images in human postoperative back muscles. SUMMARY OF BACKGROUND DATA: In a previous study, it was found that the signal intensity on T2-weighted images of the postoperative back muscles was increased in patients who had postsurgical lumbar muscle impairment, especially in those with a prolonged surgery duration. However, the specific histopathologic changes that cause the high signal intensity on T2-weighted images remain unclear. METHODS: Rats were divided into three groups: sham operation group, 1-hour retraction group, and 2-hour retraction group. Magnetic resonance imaging and histology of the multifidus muscles were examined before surgery and at 2, 7, and 21 days after surgery. RESULTS: T2-weighted imaging was more useful than T1-weighted imaging to estimate back muscle injury. The high signal intensity of the multifidus muscles on T2-weighted images remained 21 days after surgery only in the 2-hour retraction group. Histologically, the regeneration of the multifidus muscles was complete at 21 days after surgery in the 1-hour retraction group, but the regenerated muscle fibers in the 2-hour retraction group had a small diameter, and the extracellular fluid space remained large. CONCLUSION: The high signal intensity on T2-weighted images of the postoperative multifidus muscles in the regenerative phase may be due to an increased extracellular space and incomplete muscle fiber regeneration.     

Regression of a presumed meningioma with the antiestrogen agent mepitiostane. Case report

This 68-year-old woman underwent a distal gastrectomy for gastric cancer in August 1994. A presumed meningioma of the falx was found incidentally on a staging examination of the gastric cancer, but the meningioma was not treated with surgery. Instead, after gastrectomy the patient received tegafur as adjuvant chemotherapy until February 1996, when she was readmitted to the hospital because of loss of appetite and emaciation but with no recurrence of the gastric cancer. A computerized tomography scan obtained during this second admission showed no change in the meningioma. To improve her general condition, tegafur was discontinued and she was started on a course of the antiestrogen agent mepitiostane. Administration of mepitiostane for approximately 2 years resulted in a marked regression (73%) of the meningioma. This is the first reported case of a presumed meningioma that regressed as a result of use of the antiestrogen agent mepitiostane.     

Effect of N-methyl-2-pyrrolidone on skin permeation of estradiol.

N-Methyl-2-pyrrolidone (NMP) increased the skin permeation of estradiol (E2) in Yucatan micropig epidermis using a modified Franz-type diffusion cell. The addition of NMP significantly increased the fluxes of E2 from water and soybean oil. The flux and skin concentration of E2 were higher from soybean oil than from water and increased with increasing NMP concentrations in soybean oil. Correlation was observed with E2 flux and skin concentration (R(2) = 0.804) NMP enhanced E2 skin permeation because NMP made E2 skin concentration higher. Thus, NMP (10%) was added to the oily gel made by isocetyl isostearate and hydrogenated phospholipid. E2 permeation from the gel without NMP was the same as that from soybean oil suspension. The flux of E2 from the gel with NMP was 0.6 microg/h per cm(2) and might be sufficient for estrogen replacement therapy.     

Endovascular therapy for stenosis of the petrous or cavernous portion of the internal carotid artery: percutaneous transluminal angioplasty compared with stent placement

OBJECT: The effects of percutaneous transluminal angioplasty (PTA) and stent placement for stenosis of the petrous or cavernous portion of the internal carotid artery (ICA) were compared. METHODS: Twenty-four patients with symptomatic, greater than 60% stenosis of the petrous or cavernous portion of the ICA were treated using PTA or stent placement; 15 were treated with PTA and nine with stent insertion. Initial and follow-up results (> 3 months posttreatment) were compared in each group. Stenotic portions of the ICA were successfully opened in 13 of 15 patients in the PTA group, and in all nine patients in the stent-treated group. In one case in the PTA group stent delivery was attempted; however, the device could not pass through the vessel's tortuous curve, and PTA alone was performed in this case. Postoperatively, the mean stenotic ratio decreased from 72.1 to 29.6% in the PTA group, and from 75.6 to 2.2% in the stent-treated group. In four patients in the PTA group, stenoses greater than 50% were demonstrated on follow-up angiography performed at 3 to 6 months after PTA. In the stent-treated group, no restenosis was encountered, although in one case acute occlusion of the stent occurred; the device was recanalized with PTA and infusion of tissue plasminogen activator. This case was the only one of the 24 in which any neurological deficits related to the endovascular procedure occurred. Stent placement brought a greater gain in diameter than did PTA at the initial and late follow-up period; this gain was statistically significant. CONCLUSIONS: Stent placement is more effective than PTA for stenosis of the petrous or cavernous portion of the ICA from the viewpoint of initial and late gain in diameter.     

Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor

OBJECTIVE: In the present study, we delivered vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene to a rabbit model of hind limb ischemia utilizing an ex vivo method of gene transfer, and evaluated the functional performance of the developed collateral vessels. METHOD: The left femoral artery of a male Japanese White rabbit was excised to induce limb ischemia, and a section of skin was resected for culture of auto-fibroblasts. Twenty days later, the VEGF gene, bFGF gene or beta-galactosidase gene (LacZ) was adenovirally transferred to the cultured auto-fibroblasts (5x10(6) cells), and the next day, a pair of specifically infected fibroblasts (total 1x10(7) cells) was injected via the left internal iliac artery of the same rabbit. Pairs of transferred genes into the fibroblasts were as follows: LacZ/LacZ (control group), VEGF/LacZ (VEGF group), bFGF/LacZ (FGF group) and VEGF/bFGF (combination group). Twenty-eight days after cell administration, collateral development and its function were evaluated. RESULTS: Calf blood pressure ratio, resting blood flow of the left iliac artery and capillary density of ischemic muscle showed similar degrees of angiogenic effects in the VEGF and FGF groups, which were significantly greater than those in the control group. On the contrary, angiographic score, collateral conductance and smooth muscle cell (SMC)-positive vessel density in the FGF group were significantly greater than those in the VEGF group. In the combination group, collateral conductance showed synergistic effects, and in vivo blood flow and smooth muscle cell-positive vessel density revealed additive effects of VEGF and bFGF. CONCLUSION: These findings suggested that bFGF-induced collateral development exceeded VEGF-induced collateral development in the induction of arteriogenesis, and that combined gene delivery of VEGF and bFGF produced additive or synergistic effects of collateral development as compared with the effects induced by transfer of each gene alone.     

Transient lymphocytic panhypophysitis associated with SIADH leading to diabetes insipidus after glucocorticoid replacement

A 52-year-old man presented with vomiting, general fatigue and hyponatremia. His symptoms and signs were consistent with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Endocrine studies revealed hypopituitarism and administration of hydrocortisone resulted in a marked polyuria. The patient was diagnosed as masked diabetes insipidus. The lymphocytic hypophysitis was also diagnosed on the basis of MRI findings and anti-pituitary antibody. Six months later, these abnormalities disappeared. Diabetes insipidus may exist in a case of hyponatremia due to contrastive SIADH. Such patients may recover spontaneously and careful follow-up is required, avoiding a long-term treatment by monotonous continuation of hormonal replacement.