Functional analysis of the tissue-engineered stomach wall

We have established a method for in situ tissue engineering of the stomach in a canine model using an acellular collagen scaffold graft. The current study was conducted to evaluate the functional aspects of the tissue-engineered stomach wall. The anterior wall of the stomach in beagle dogs was replaced with a collagen sponge scaffold measuring 4 x 4 cm. At 16 weeks after implantation, the animals were sacrificed and the stomach specimens were evaluated immunohistochemically and physiologically. Regeneration of the proton pump and thin muscle layer, which are essential for mechanical and chemical digestion by the stomach, was observed in the tissue-engineered gastric tissue. However, acetylcholine-induced contraction was not observed in the tissue-engineered stomach wall. Although there is still room for improvement, the tissue-engineered stomach wall had a highly organized structure, and it is anticipated that this approach could eventually become an alternative for stomach reconstruction after gastrectomy.     

Magnetoencephalographic localization of multiple seizure foci for surgical treatment of intractable frontal lobe epilepsy: confirmation with intra-operative electrocorticography

A successfully treated case of intractable FLE, of which preoperative magnetoencephalography (MEG) provided multiple spike localization and intraoperative corticogram (ECoG) confirmed the resection area. A 22-year-old male patient, with a history of subdural abscess at the age of 14 years, had suffered frequent simple (SPSs) and complex partial seizures (CPSs) and falling attacks since the age of 16 years. Although he underwent corpus callosotomy at the age of 17 years, additional surgical treatment was considered because of intractable and more frequent SPSs and CPSs. Magnetic resonance (MR) imaging demonstrated diffuse lesions in the right frontal lobe. Although, both interictal and ictal electroencephalography (EEG) failed to show focal epileptogenic localization, interictal MEG localized several clusters over the multiple anatomical lesions in the right prefrontal and frontal opercular regions. The patient underwent right fronto-temporal craniotomy, and anterior frontal lobectomy, followed by lesionectomy of the premotor area based on the intraoperative ECoG findings. The ECoG localized frequent spike discharges over the right prefrontal, frontal operculum and premotor cortices, which showed good correspondence with the MEG findings. MEG can be a useful noninvasive method for presurgical evaluation of intractable FLE.     

Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis.

Previously, we discovered that periodontal ligament (PDL) cells not only support osteoclastogenesis through cell-to-cell contact, but also inhibit the formation of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells by a producing soluble factor(s). Furthermore, PDL cells express both receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) messenger RNA (mRNA). Clinically, "ankylosed teeth," which lack periodontal ligament, cannot be moved with orthodontic tooth treatment. From this, we hypothesized that PDL cells under mechanical stress should play a pivotal role in osteoclast formation during orthodontic tooth movement. This study examined how mechanical stress affects the osteoclastogenesis-supporting activity of PDL cells. PDL cells were compressed continuously and then cocultured with peripheral blood mononuclear cells (PBMCs) for 4 weeks. PDL cells under mechanical stress up-regulated osteoclastogenesis from PBMCs. Furthermore, the expression of RANKL mRNA and protein in PDL cells increased with compressive force in parallel with the change in the number of osteoclasts. In addition, cyclo-oxygenase 2 (COX-2) mRNA expression was induced by compressive force, and indomethacin inhibited the RANKL up-regulation resulting from compressive force. PDL cells under compressive force exhibited significantly increased prostaglandin E2 (PGE2) production in comparison with control PDL cells. Exogenous PGE2 treatment increased RANKL mRNA expression in PDL cells. Interestingly, OPG expression remained constant throughout compressive force or PGE2 treatment. In conclusion, compressive force up-regulated RANKL expression in PDL cells. Furthermore, RANKL up-regulation in mechanically stressed PDL cells was dependent on PGE2.     

Development of hyperthyroidism in a patient with idiopathic nephrotic syndrome

We present a 13-year-old boy who developed hyperthyroidism during the clinical course of idiopathic nephrotic syndrome treated with glucocorticoid. He had a second relapse of minimal change nephrotic syndrome, and complete remission of nephrotic syndrome was achieved immediately with oral glucocorticoid. However, when the steroid dosage was reduced, signs of hyperthyroidism such as systolic hypertension and tachycardia were observed. Laboratory findings revealed thyroid-stimulating hormone (TSH) below 0.05 μU/ml, free tri-iodothyronine of 16.1 pg/ml, free thyroxine of 5.6 ng/dl, and anti-TSH receptor antibody of 90%. Thus, a diagnosis of hyperthyroidism was made and treatment with thiamazol was started. Massive proteinuria may decrease the activity of hyperthyroidism due to urinary loss of thyroid hormones. A decrease in glucocorticoid dosage may also be involved in the development of hyperthyroidism due to a reduced immunosuppressive effect. Received: 11 July 2001 / Revised: 22 October 2001 / Accepted: 27 November 2001     

Functional Mediastinal Parathyroid Cyst: Report of a Case

We report herein a rare case of a functional mediastinal parathyroid cyst. A mediastinal tumor was detected by a chest X-ray film and subsequent computed tomography (CT) scan in a 68-year-old woman who was asymptomatic. Biochemical examination revealed that her serum calcium and intact-parathyroid hormone (i-PTH) levels were above the normal range. The findings of chest CT and magnetic resonance imaging suggested a cystic mass. The mass, which adhered tightly to its surrounding structures, was resected through a median sternotomy. The patient had an uneventful postoperative course, and her serum calcium and i-PTH levels rapidly returned to within the normal range. Received: March 21, 2001 / Accepted: September 11, 2001     

Inflammatory Malignant Fibrous Histiocytoma of the Gallbladder: Report of a Case

We describe herein a case of inflammatory malignant fibrous histiocytoma (IMFH) of the gallbladder that subsequently metastasized to the ascending colon and later to the stomach. A 70-year-old Japanese man with a palpable mass in the right upper quadrant of the abdomen was referred to our hospital for investigation and treatment. Laboratory data showed severe leukocytosis and elevated serum granulocyte colony-stimulating factor (G-CSF) concentrations. A laparotomy was performed, and the tumor was excised en bloc with the gallbladder and part of the liver bed. Histopathologically, the tumor was composed of ordinary malignant fibrous histiocytoma (MFH) components characterized by pleomorphic tumor cells, bizarre giant cells, and conventional spindle cells in a storiform growth pattern, as well as a xanthogranulomatous component, including inflammatory cells, foamy histiocytes, and plasma cells. Immunohistochemical study revealed that the pleomorphic tumor cells and bizarre giant cells were positive for antibodies against α₁-antitrypsin and α₁-antichymotrypsin. The final pathologic diagnosis was IMFH. The tumor cells were diffusely positive for anti-G-CSF monoclonal antibody, and the inflammatory reaction subsided immediately after tumor resection, strongly suggesting that the primary tumor cells produced G-CSF. This patient is still alive with no signs of recurrence more than 3 years after his primary operation, which to our knowledge is the longest survival period ever reported. Therefore, visceral IMFH is manageable in some cases by resecting the primary and isolated metastatic lesions. Received: October 11, 2000 / Accepted: May 15, 2001     

Diurnal variation of human corneal curvature in young adults

PURPOSE: To elucidate the diurnal variation of human corneal curvature with regard to gender and menstrual cycle. METHODS: Changes in corneal curvature and intraocular pressure (IOP) were measured over 24 hours in 14 young adults using corneal topography and a non-contact tonometer. In study 1, seven males and seven females (after menses) were measured. In study 2, four females out of the seven volunteers who participated in study 1 were measured again during menses. RESULTS: The females after menses showed a remarkable diurnal variation throughout 24 hours. A significant difference between the light-wake periods and dark-sleep periods of 0.83 +/- 0.15 D was found (P < .01). Corneal curvature was significantly flatter during menses than after menses in the light-wake period (P < .05). In the males, no significant diurnal change (0.21 +/- 0.12 D) was measured in corneal curvature. CONCLUSIONS: Diurnal variation of corneal curvature was significant, approximately 0.83 D in young females after menses, and corneal curvature became flatter during menses in young females. Diurnal variation of corneal curvature is an important parameter for planning refractive surgery and contact lens wear.     

A novel mutation of the type 1 optic atrophy(OPA1) gene in a Japanese family with OPA1

PURPOSE: To report a novel mutation of the type1 optic atrophy(OPA1) gene in a Japanese family with OPA1 and to describe the clinical features of this family. METHODS: Standard ocular examinations were performed on the proband and his two affected sons. The DNA sequence of all exons and splice sites of the OPA1 gene was determined to detect mutations. RESULTS: The proband and his sons had a heterozygous mutation of the OPA1 gene in the third nucleotide of intron 12(IVS12 + 3A-->T). Clinically, each patient had reduced visual acuity(onset within the first 6 years of life) and optic nerve pallor. The proband showed a central scotoma and generalized dyschromatopsia. This is the first report of OPA1 gene mutation in Japanese patients with familial optic atrophy. CONCLUSIONS: A mutation of the OPA1 gene was detected in a Japanese family with OPA1, which follows the same pattern as reported in Western countries. It is suggested that mutations of the OPA1 gene contribute to the development of optic nerve atrophy regardless of ethnic groups. Screening for the OPA1 gene mutation will be useful for diagnosis of OPA1 in Japanese patients.     

Anti-emetic activity of the novel nonpeptide tachykinin NK1 receptor antagonist ezlopitant (CJ-11,974) against acute and delayed cisplatin-induced emesis in the ferret

The anti-emetic effects of a novel tachykinin NK(1) receptor antagonist, ezlopitant ((2S,3S-cis)-2-diphenylmethyl)- N-[(2-methoxy, 5-isopropylphenyl)methyl]-1-azabicyclo- [2.2.2]octan-3-amine), were investigated in ferrets. Ezlopitant inhibited [(3)H]substance P ([(3)H]SP) binding to the human, guinea pig, ferret and gerbil NK(1) receptors (K(i) = 0.2, 0.9. 0.6 and 0.5 nmol/l, respectively), but had no affinity to NK(2) and NK(3) receptors up to 1 micromol/l. Ezlopitant also inhibited SP-induced contraction of guinea pig trachea with a pA(2) value of 7.8, but had no effects on the baseline tension and maximum contractile response. In ferrets, ezlopitant, either orally (0.03-3 mg/kg) or subcutaneously (0.3-3 mg/kg), prevented acute retching and vomiting responses induced by intraperitoneal injection of cisplatin (10 mg/kg). In addition, repeated subcutaneous injection of ezlopitant significantly inhibited delayed retching and vomiting responses that occurred in ferrets treated with the lower dose of cisplatin (5 mg/kg, i.p.). Ezlopitant (0.1-1 mg/kg, s.c.) also produced a dose-dependent inhibition of hindpaw tapping induced by intracerebroventricular injection of [Sar(9),Met(O(2))(11)]SP in gerbils, which is known to be mediated by NK(1) receptors in the brain. These findings indicate that ezlopitant is a potent and selective NK(1) receptor antagonist, and that it inhibits both acute and delayed emetic reactions induced by cisplatin in ferrets via acting on NK(1) receptors in the central nervous system.