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.     

Finger bougie method compared with pyloroplasty in the gastric replacement of the esophagus

To elucidate the necessity of pyloroplasty for the gastric tube through the posterior mediastinum in esophageal surgery, gastric emptying and duodenogastric reflux (DGR) were evaluated in 16 cases undergoing an anterior pylorectomy (group P) and in 16 cases treated by the finger bougie method (group F). First, the obstruction and reflux symptoms were examined based on a patient questionnaire using a brief scoring system. The median value of the symptom score showed the patients in P to have more symptoms than those in F; however, the difference was not significant (8.0 vs 6.0). Secondly, the swallowed Tc O₄ ⁻ (85 MBq) was counted using a gamma camera at three sites on the sternal bone in the upright position based on a gastric transit scintigram. Both the descending time of the RI peak and the clearance rates were similar between the two groups. Thirdly, intragastric 24-h pH monitoring was carried out. Antimony pH sensors were anchored 5 and 15 cm below the esophagogastrostomy. We could not find any difference between the two groups in both the % time pH>4 and %time pH>7. These findings thus revealed no big difference between groups P and F. The finger bougie method to drain the vagotomized posterior mediastinal stomach was found to achieve results similar to conventional pyloroplasty, while it was also simpler and safer.     

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.     

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis. BACKGROUND: 22-Oxacalcitriol (OCT) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PTH) secretion in uremic rats. This study was performed to examine the long-term effect of intravenously administered OCT on high-turnover bone disease in model rats of slowly progressive renal failure. METHODS: Slowly progressive renal failure rats were made by a single injection of glycopeptide isolated from rat renal cortical tissues. At 250 days, glycopeptide-induced nephritis (GN) rats were divided into three groups with the same levels of serum creatinine and PTH, and they received either OCT (0.03 or 0.15 microg/kg body wt) or vehicle given intravenously three times per week for 15 weeks. RESULTS: Renal function of GN rats deteriorated very slowly but progressively, as assessed by the increase of serum creatinine concentration. At sacrifice, serum PTH levels, bone formation markers, bone resorption markers, and fibrosis volume were significantly elevated in vehicle-treated GN rats compared with those of sham-operated rats, suggesting the development of high-turnover bone disease with osteitis fibrosa. In contrast, in the GN-OCT 0.15 microg/kg group, these high PTH levels and high-turnover bone and fibrosis were significantly decreased. Such amelioration of bone abnormalities by OCT was not accompanied by either hypercalcemia or further deterioration of renal function. CONCLUSIONS: These data indicate that OCT may be a useful and safe agent not only for the suppression of PTH, but also for the amelioration of osteitis fibrosa and high-turnover bone without causing hypercalcemia in chronic dialysis patients.     

Neurovascular developmental interaction: a specific form of vascular maldevelopment in the malformed brain

The process of the development of the intracranial vessels was studied by means of immunohistochemical analysis of factor VIII in normal and exencephalic chick fetuses. The results revealed that the development of blood vessels in exencephalic brain was far advanced beyond the norm, with intense immunoreactivity to factor VIII on postincubation day 16 exceeding that on day 21 in normal controls. Compared with results regarding the direction of the overgrowth in the neuronal maturation process in the previous study using the chick exencephaly model, the findings of overmatured blood vessels were compatible with NSE- and somatostatin-positive elements that appeared especially in the overgrowth foci. The results of the present study suggested the pathogenic development of the area cerebrovasculosa in the neural placode as a phenomenon consequent upon hypervascularization in response to neuronal overgrowth, as seen in human cases of exencephaly or anencephaly. We emphasize the significance of this specific phenomenon in the development of the fetal central nervous system, namely neurovascular developmental interaction.     

Use of YAG laser combined with mucosal suturing for the treatment of polypoid vocal cord]

To improve low-pitched voices in cases with polypoid vocal cords, YAG laser irradiation combined with a mucosal suturing technique was attempted in 9 female cases with severe polypoid changes in their vocal cords. A YAG laser beam (5 to 10 W) was used to irradiate the upper surface of the polypoid vocal cord. The polypoid content of the cord was gradually coagulated, and the free edge of the cord appeared to slide up toward the burned area. The polypoid content was then removed and squeezed through an open wound made in the burned area using a conventional method. Bleeding was successfully controlled using the laser. After the excessive mucosal margin was trimmed and the contour of the vocal cord was adjusted, the wound was closed by 7-0 monofilament absorbable suture. Suturing was relatively easy because the mucosal edge was also coagulated. Postoperative evaluations of voice quality revealed an improvement in the GRBAS scale of voice quality as well as an elevation in voice pitch and an upwards shift in the voice range in all cases.     

Changes in patterns of left ventricular hypertrophy after aortic valve replacement for aortic stenosis and regurgitation with St. Jude Medical cardiac valves

In this study, we analyzed the extent and pattern of regression of left ventricular (LV) hypertrophy after aortic valve replacement in patients with aortic stenosis (AS) and compared the results with those of another group of patients with aortic regurgitation (AR). Seventy patients who underwent isolated aortic valve replacement were divided into 2 groups. Group 1 was comprised of 29 patients who underwent aortic valve replacement for aortic stenosis, and Group 2 of 41 patients who underwent aortic valve replacement for aortic regurgitation. A third group of 10 healthy subjects served as a healthy control group. Echocardiographic studies were done before the operation and 5 years postoperatively. At follow-up, a significant reduction in the left ventricular mass was found in both groups, but it remained significantly greater than in the healthy control group. The ratio of LV wall thickness to radius (th/r) in Group 1 decreased significantly, and at follow-up it was within the normal value. In Group 2, the th/r ratio increased, and at follow-up it was within the normal value. After aortic valve replacement, the wall thickness remained significantly greater than normal for patients with AS, and the chamber radius remained significantly greater than normal for patients with AR. For these reasons, LV hypertrophy still existed in both groups at postoperative follow-up. The actuarial survival rate was 85.3% at 16 years for Group 1 and 83.4% at 18 years for Group 2. There was no significant difference in the long-term survival rates between the 2 groups. Actuarial freedom from valve-related events was 91.9% at 16 years for Group 1 and 82% at 18 years for Group 2. There was no significant difference in the valve-related event free curves between groups. After 5 years of follow-up, th/r reached normal for both groups, indicating remodeling of the LV geometry after aortic valve replacement.     

Prognostic significance of loss of heterozygosity on chromosome 9p21–22 in human esophageal cancer

Background Deletions involving chromosome 9p21, on which the tumor suppressor genep16/MTS1 is located, have been noted in esophageal cancer. We investigated the relationship between the deletion of chromosome 9p21–22 and the clinical features of esophageal cancer. Methods We examined the loss of heterozygosity (LOH) on chromosome 9p21–22 in 56 esophageal cancers using polymerase chain reaction (PCR) analysis and 2 microsatellite markers (RPS6 and IFNA). Results In 18 out of 50 informative cases (36%), LOH had occurred at 1 or 2 loci on chromosome 9p21–22. We found no relationship between LOH on chromosome 9p21–22 and patient sex, age tumor length, location, histologic differentiation, depth of tumor invasion, the extent of lymph node metastasis, histologic stage, or curability. Among 35 patients without an absolute noncurative resection, the mean survival of 11 patients with LOH on chromosome 9p21–22 was 19.3 months, compared with 42.3 months for 24 patients with a normal allele; thus, the survival rate of those with LOH was significantly lower than that of patients without LOH on chromosome 9p21–22 (log-rank test;P=0.03). Conclusion These data suggest that LOH on chromosome 9p21–22, on which the cell-cycle regulatorp16/MTS1 gene is located, may be related to cancer development, and probably can serve as a clinical marker for evaluating a patient's prognosis.