Expression of the receptor for pituitary adenylate cyclase-activating polypeptide (PAC1-R) in reactive astrocytes

We generated transgenic mice that express an enhanced green fluorescent protein (EGFP) under the control of the mouse glial fibrillary acidic protein (GFAP) promoter. In one of the transgenic lines, the green fluorescence of EGFP was undetectable in almost all of the brain regions, including the neocortex, in untreated animals. However, when reactive astrogliosis was induced by cortical stab wounding, the strong fluorescence of EGFP was observed around the needle track but was not found in the corresponding area of the contralateral hemisphere. The EGFP-expressing cells had the morphological features of reactive astrocytes such as thick processes. The EGFP-expressing cells were found to overlap with the astroglial marker GFAP, but not with the microglial marker CD11b or the neuronal marker NeuN. Furthermore, there were some EGFP-expressing cells that expressed vimentin-like immunoreactivity, the specific marker for reactive astrocytes. These results strongly suggest that the EGFP-expressing cells are reactive astrocytes, but not resting astrocytes. Using these transgenic mice, immunostaining for the PAC1 receptor (PAC1-R) was performed. PAC1-R, which is a pituitary adenylate cyclase-activating polypeptide (PACAP)-specific receptor, binds PACAP, which is known to have a wide variety of functions. An immunohistochemical study revealed the localization of PAC1-R in reactive astrocytes visualized with EGFP around the needle track at 5 days postsurgery.     

Demonstration of immunoreactive somatostatin-like substance in villi and decidua in early pregnancy.

With the use of the radioimmunoassay for growth hormone--releasing inhibiting factor (GIF), it was found that measurable amounts of GIF-like substance existed in the chorionic villi and decidua of pregnant women. The indirect immunofluorescent method revealed that the higher intensity of GIF-like immunofluorescence was presented in cytotrophoblasts rather than in syncytiotrophoblasts of the villi and in stromal cells of the decidua.     

Epidemiologic Studies on mumps. II. Prospective, Periodic Surveillance on Mumps in Three Different Areas

Prospective, periodical sero-epidemiological surveillance on mumps was carried out in three different populations in Aichi prefecture. 1) In a newly developed residental quarter full of big apartment buildings, where heavy population density burst has been occurring, mumps has been observed as an endemic disease. Serologically, almost all the children under six years old has experienced mumps infection in such an area. 2) In an old city with stable population dynamics, mumps outbreaks have been taken place pediodically. The results of serosurvey suggested that the periodic outbreaks occurred when more than 60–70% of the children became susceptible, regardless of seasons. 3) In a relatively isolated small town, mumps epidemics has not been observed for many years and when the disease is introduced into the community however, large outbreak develops in the town.     

Pulmonary metastasectomy for metachronous metastasis of esophageal cancer after esophagectomy

Background and objective

Pulmonary metastasectomy is a standard therapy for some types of metastatic lesions in the lung. Although the prognosis for esophageal cancer patients with pulmonary metastasis is poor, it has been reported that some post-esophagectomy patients have good prognosis after pulmonary metastasectomy. We investigated the role of resecting pulmonary metastases arising from esophageal cancer at our institution.

Patients and methods

Seven patients with primary squamous cell carcinoma or adenocarcinoma of the thoracic esophagus who underwent resection of metachronous pulmonary metastases at our institution between 2006 and 2012 were identified from a retrospective database. All patients had undergone curative resection of their primary esophageal carcinoma.

Results

Six patients had unilateral and solitary lung metastasis. One patient presented with one metastatic lesion on each side, and he underwent 4 metastasectomy for pulmonary metastasis 3 times. There was no perioperative morbidity or mortality. The disease-free interval after esophagectomy ranged from 191 to 559 days (median, 463 days). Survival after pulmonary metastasectomy ranged from 357 to 3191 days (median, 1803 days). Three patients received systemic chemotherapy before metastasectomy. Currently, 5 patients are alive without evidence of recurrent disease.

Conclusion

Pulmonary metastasectomy may be acceptable as a part of multimodal treatment for solitary metachronous pulmonary metastasis in esophageal carcinoma.

     

Attenuation of the activated mammalian target of rapamycin pathway might be associated with renal function reserve by a low-protein diet in the rat remnant kidney model

The mammalian target of rapamycin (mTOR), a regulator of cellular protein synthesis and cell growth, plays an important role in the progression of renal hypertrophy and renal dysfunction in experimental chronic kidney disease models. Because the mTOR activity is regulated by nutrients including amino acids, we tested the hypothesis that the renoprotective effect of a low-protein diet (LPD) might be associated with the attenuation of the renal mTOR pathway. In this study, 5/6 nephrectomized rats were fed an LPD or a normal protein diet (NPD), and a number of rats that were fed an NPD received rapamycin (1.0 mg kg⁻¹ d⁻¹), a specific inhibitor of mTOR. After 6 weeks, renal tissue was collected to evaluate the activity of the mTOR pathway and histologic changes. The phosphorylation of p70S6k, a kinase in the downstream of mTOR, was significantly higher in the NPD-fed rats that showed progressive renal dysfunction than in the sham-operated rats (NPD). The LPD attenuated the excessive phosphorylation of p70S6k concomitant with reduced proteinuria and improved renal histologic changes in the 5/6 nephrectomized rats. The effects of the LPD were similar to the effects of rapamycin. The expression of phosphorylated p70S6k was significantly correlated with proteinuria (r² = 0.63, P < .001), the glomerular area (r² = 0.60, P < .001), and the number of phosphorylated Smad2-positive cells in the glomerulus (r² = 0.26, P < .05) of these rats. These results suggest that the preventive effect of an LPD on the progression of renal failure is associated with attenuation of the activated mTOR/p70S6k pathway in the rat remnant kidney model.     

Association between Dietary Fat Intake and Hyperuricemia in Men with Chronic Kidney Disease

Despite a close relationship between chronic kidney disease (CKD) and uric acid level, few studies have examined the relationship between uric acid level and fat intake by kidney function status. Therefore, we investigated the association between dietary fat intake and hyperuricemia with and without decreased kidney function in males living in Shika Town, Ishikawa Prefecture, Japan. This study included 361 males with a mean age of 60.7 years. Dietary fat and fatty acid intakes were evaluated using the brief-type self-administered diet history questionnaire. Reduced kidney function was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m², while hyperuricemia was defined as a serum uric acid level >7.0 mg/dL. A two-way analysis of covariance showed that saturated fatty acid (p = 0.026), monounsaturated fatty acid (p = 0.014), and polyunsaturated fatty acid (p = 0.022) were significantly lower in the high uric acid group than in the normal uric acid group. In multiple logistic analysis stratified by renal function, lipid intake was negatively associated with hyperuricemia in the low eGFR group. These findings suggest that higher dietary lipid/fatty acid intake may be effective in the prevention and treatment of hyperuricemia in men with CKD.     

High efficacy of pleurodesis using OK-432 for controlling intractable pneumothorax associated with pulmonary lymphangioleiomyomatosis]

We evaluated the efficacy of pleurodesis using OK-432 (Picibanil) for the treatment of pneumothorax associated with pulmonary lymphangioleiomyomatosis (LAM). Seven episodes of pneumothorax in five patients with LAM were treated with pleurodesis using OK-432. First, all patients underwent tube thoracostomy drainage. After drainage, 5 or 10 KE of OK-432 was administered via the tube. If incomplete lung expansion or a continuous air leak occurred, an additional 5 KE of OK-432 was administered. Of the five patients, two developed pneumothorax for the first time and three had a history of previous pneumothorax. The mean total dose of OK-432 administered was 13.6 KE, and the mean period of tube drainage was 11 days. The only recurrence of ipsilateral pneumothorax after OK-432 pleurodesis was observed seven years and eight months later in association with chronic respiratory failure in one patient. This patient was successfully treated with repeated pleurodesis using OK-432 during mechanical ventilation, and no recurrence has developed in the eight years since then. The main side effects of the procedure with OK-432 were fever and chest pain, which were well controlled by non-steroidal anti-inflammatory drugs. The study concluded that pleurodesis with OK-432 was an effective and safe treatment for intractable and recurrent pneumothorax associated with LAM.     

Neuroprotective effects of progesterone in traumatic brain injury: blunted in vivo neutrophil activation at the blood-brain barrier

Background

Progesterone (PRO) may confer a survival advantage in traumatic brain injury (TBI) by reducing cerebral edema. We hypothesized that PRO reduces edema by blocking polymorphonuclear (PMN) interactions with endothelium (EC) in the blood-brain barrier (BBB).

Methods

CD1 mice received repeated PRO (16 mg/kg intraperitoneally) or vehicle (cyclodextrin) for 36 hours after TBI. Sham animals underwent craniotomy without TBI. The modified Neurological Severity Score graded neurologic recovery. A second craniotomy allowed in vivo observation of pial EC/PMN interactions and vascular macromolecule leakage. Wet/dry ratios assessed cerebral edema.

Results

Compared with the vehicle, PRO reduced subjective cerebral swelling (2.9 ± .1 vs 1.2 ± .1, P < .001), PMN rolling (95 ± 1.8 vs 57 ± 2.0 cells/100 μm/min, P < .001), total EC/PMN adhesion (2.0 ± .4 vs .8 ± .1 PMN/100 μm, P < .01), and vascular permeability (51.8% ± 4.9% vs 27.1% ± 4.6%, P < .01). TBI groups had similar a Neurological Severity Score and cerebral wet/dry ratios (P > .05).

Conclusions

PRO reduces live pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO effects on the microcirculation warrant further investigation.     

BRUSHITE IN FIBROUS DYSPLASIA OF THE JAW BONE

Crystals associated with the maxillary bone in a case of fibrous dysplasia were investigated histopathologically, crystallo-graphically and by infrared absorption spectroscopy. Light microscopically, the crystals showed a transparent and plate-like appearance, and were revealed to be piled, incomplete monoclinic structures up to 250μm in size by scanning electron microscopy. These crystals were identified as brushite, dicalcium phosphate dihydrate CaHP0₄ 2H₂0, by X-ray microdiffraction and infrared absorption spectroscopic analysis. From consideration of the equilibrium of brushite, it was assumed in this case that inflammation had occurred initially and that the tissue fluid conditions at the site of the lesion had deviated from normal, eventually resulting in the deposition of brushite crystals on the bone apatite. From a crystallographic view point, the mode of occurrence of brushite suggested that the bone at the lesion site would not recover through normal healing. ACTA PATHOL. JPN. 37: 1699-1705, 1987.