Pathologic features of superficial esophageal squamous cell carcinoma with lymph node and distal metastasis

BACKGROUND: Endoscopic mucosal resection (EMR) is a less invasive localized treatment for patients with esophageal carcinoma. However, indications for EMR use in cases of superficial esophageal carcinoma are controversial. The authors evaluated histopathologic risk factors for lymph node metastasis and recurrence. METHODS: In the specimens resected, the authors examined depth, the superficial area and the area attached to or infiltrating the lamina muscularis mucosa. RESULTS: The authors found that the superficial area and the attached or infiltrated area reflected the depth of the tumor. However, there was a recurrence of esophageal carcinoma even in m3 cases attached only to the lamina muscularis mucosa. CONCLUSIONS: The authors concluded that ml and m2 esophageal carcinoma had almost no risk of lymph node metastasis and recurrence no matter how extensive the superficial area. In addition, sm2 and sm3 carcinoma have a high frequency of lymph node metastasis and recurrence. M3 and sm1 carcinoma run the risk of lymph node metastasis and recurrence however small the superficial area and the area attached to or infiltrating the lamina muscularis mucosa. Treatment strategies for patients with superficial esophageal carcinoma, including EMR, should take the above findings into account.     

Estrogen blocks 3-nitropropionic acid-induced Ca2+i increase and cell damage in cultured rat cerebral endothelial cells

Systemic administration of 3-nitropropionic acid (3-NPA, a mycotoxin) induces brain damage accompanied by disturbance in the blood-brain barrier (BBB). Since the endothelial cells are important components of the BBB and the first target of a systemic intoxication, in the present study, the effect of 3-NPA on primary cultured rat brain endothelial cells (rBECs) was examined by studying intracellular Ca(2+) ([Ca(2+)](i)) response using imaging techniques with fura-2. rBECs were prepared using a method of Kis et al. [Eur. J. Pharmacol. 368 (1999) 35-42] and Szabo et al. [Neurobiology 5 (1997) 1-16]. Almost all cells were immunoreactive to antibody against the factor VIII-related antigen (von-Willebrand factor). They showed a typical dose-dependent increase of [Ca(2+)](i) in response to ATP or bradykinin. Low concentrations of 3-NPA (1.7 mM, 3.4 mM) caused no changes, and a medium concentration (6.8 mM) increased the [Ca(2+)](i) gradually and progressively, and the increase was reversed incompletely back to the resting level after washing. A high concentration (13.6 mM) increased the [Ca(2+)](i) irreversibly. These elevations of [Ca(2+)](i) were absent in a Ca(2+)-free medium. In endothelial cells treated with 17beta-estradiol (above 10(-5) M) or with a selective estrogen receptor modulator, tamoxifen (5 x 10(-7) M), no elevation of [Ca(2+)](i) was observed with 3-NPA treatment. The response to ATP was impaired after application of 3-NPA, but it was preserved by cotreatment with 17beta-estradiol or tamoxifen. An estrogen receptor antagonist ICI 182,780 inhibited these effects by 17beta-estradiol or tamoxifen. Lysosomal neutral red uptake and TUNEL experiments revealed the necrotic but not apoptotic cell death at least in this acute stage. Data indicate that a medium to high concentration of 3-NPA induces damage on rBECs as revealed by an accumulation of [Ca(2+)](i), but the damage was protected by cotreatment with 17beta-estradiol or tamoxifen, suggesting that estrogen may be protective for the brain vascular damage via estrogen receptor.     

Vasopressin receptor knockout mice as an animal model of psychiatric disorders]

Arginine vasopressin (AVP) is a neurohypophyseal peptide best known as an antidiuretic hormone. AVP receptors have been classified into three subtypes: V1a, V1b, and V2 receptors. The V1a receptor (V1aR) and V1b receptor (V1bR) are widely distributed in the central nervous system, including the cortex and hippocampus. In the present study, we examined the performance of V1aR or V1bR knockout (KO) mice compared to wild-type (WT) mice in behavioral tests. V1aR KO mice exhibited impairments of spatial learning (eight-arm radial maze), prepulse inhibition (PPI) and social behavior in comparison to WT mice. On the other hand, V1bR KO mice also displayed impairments of PPI and social behavior. These results suggest that V1aR and V1bR may be involved in psychiatric disorders associated with impairments of sensorimotor gating and social behavior such as schizophrenia and autism.     

Further studies on the synthesis of A-form monoamine oxidase

The relation between precursors and restoration of A-form MAO activity in rat liver after administration of clorgyline to rats was investigated by measuring the rates of recovery of A-form MAO activity after treatment with the inhibitor. The half-lives of mitochondrial and microsomal A-form MAO were estimated as 3.5 and 2.0 days, respectively. MAO activity and the amount of MAO molecules were completely restored within 14 days. However the values attained did not exceed the control values in a period of 14 days. Clorgyline plus cycloheximide or chloramphenicol did not prevent the recovery of MAO activity in the microsomes, but did not delay the appearance of enzyme activity in the mitochondria. A and B-form-like MAO were also observed in the microsomal and supernatant fractions, with clorgyline as inhibitor. These results suggest that the microsomal enzyme is a precursor of the mitochondrial enzyme, that the levels of A-form and B-form MAO are regulated genetically, and that the two forms of MAO may be synthesized separately.     

Ipsilateral mamillary body atrophy after infarction of the posterior cerebral artery territory: MR imaging

We describe herein magnetic resonance (MR) features of ipsilateral mamillary body atrophy after infarction of the posterior cerebral artery (PCA) territory. During the period May 2000 through July 2004, 13 patients with infarction of the PCA territory underwent cranial MR imaging in the chronic stage. Two 1.5-T scanners were used to obtain axial T1- and T2-weighted images with conventional spin-echo and fast spin-echo pulse sequences, respectively. The slice thickness was 6 mm, with a 2-mm interslice gap. Five of the 13 patients with PCA territory infarction had ipsilateral mamillary body atrophy. However, this asymmetry of the mamillary bodies was unclear in two of the five patients because of the thickness of the axial image slices. All five patients had a temporo–parieto–occipital infarction. The remaining eight patients had a parieto–occipital or an occipital infarction. Unilateral transneuronal mamillary body degeneration after infarction of the ipsilateral PCA territory including the posteromedial temporal lobe can be detected on conventional thick axial MR images.     

Mesenteric fibromatosis successfully resected with duodeno-jejunectomy and nephrectomy

We report a rare case of intra-abdominal fibromatosis of the jejunal mesentery. A 71-year-old man, who was incidentally diagnosed with left hydronephrosis, was found to have a tumor near the duodeno-jejunal junction. The tumor appeared to invade the intestinal wall and was obstructing the left ureter. The tumor was indefinite in diagnosis preoperatively. The patient underwent an en-bloc excision of the tumor by a partial duodeno-jejunectomy combined with a left nephrectomy. Microscopic examination of the tumor showed that non-dysplastic fibroblasts proliferating in the jejunal mesentery had infiltrated into the adjacent small intestines and ureter, resulting in a diagnosis of intra-abdominal fibromatosis. This diagnosis was supported by findings of immunohistochemical analyses showing positive staining for vimentin and smooth muscle actin and negativity for keratin, CD34, C-kit and S-100. To our knowledge, this is the first documented case of intra-abdominal fibromatosis of the jejunal mesentery completely resected with the operative procedure described herein. In cases of a preoperatively undiagnosed retroperitoneal or mesenteric tumor that invades adjacent structures, it is important to consider intra-abdominal fibromatosis as a possible differential diagnosis. This may be helpful in planning the appropriate therapeutic strategies including extended multi-organ resection in selected patients.     

Considerable multiple esophageal carcinoma. Implications of a new clinical entity

BACKGROUND/AIMS: The multiple occurrence of primary squamous cell carcinoma of the esophagus is often observed, and most such occurrences are double cancers. There have also been some cases with three or more intra-esophageal cancers, however, no detailed clinicopathologic study has yet been performed in the literature. METHODOLOGY: Two hundred and fifty patients of primary esophageal squamous cell carcinoma without preoperative treatment that underwent esophageal resection were re-evaluated by serial histopathologic investigations and we analyzed the data of ten patients with three or more intraesophageal cancers. RESULTS: The clinical and histopathologic characteristics were as follows; 1) all but one of the cases were male, 2) all patients had a history of both heavy smoking and drinking but only one case had a family history of esophageal cancers among their siblings, 3) the depth of invasion in the carcinomas was restricted to within the submucosal layer of the esophageal wall, which was defined as superficial esophageal carcinoma, almost all (90%) of the cases accompanied esophageal squamous epithelial dysplasia. CONCLUSIONS: Based on these prominent characteristics of considerable multiple intra-esophageal cancers, a new clinical entity of "esophageal field cancers" could thus be suggested.     

Characteristics of behavioral abnormalities in alpha1d-adrenoceptors deficient mice

To investigate the functional role of alpha1d-adrenergic receptor (alpha1d-AR) in the CNS, we have generated mutant mice lacking the alpha1d-AR using a gene targeting approach and examined in detail the effects of alpha1d-AR knockout mice on motor function, sensory function, and learning and memory. alpha1d-AR knockout mice showed better motor coordination at the highest rotating speed of the rotarod performance and stronger muscle tone using the traction meter, but their locomotor activity and swimming ability in the water maze were not affected. In the water maze requiring reference memory, alpha1d-AR knockout mice showed normal spatial learning. In the Y-maze task requiring working memory or attention, alpha1d-AR knockout mice displayed an impaired spontaneous alternation performance. The alpha1d-AR knockout mice tended to display lower levels of acoustic startle responses than the wild-type group at lower pulse intensities, although the acoustic prepulse inhibition was not impaired in the alpha1d-AR knockout mice. Furthermore, the NMDA receptor antagonist, MK-801-induced deficits of acoustic prepulse inhibition were not observed in the alpha1d-AR knockout mice. These results clearly demonstrate that the alpha1d-AR receptor plays an important role in the process of auditory sensory function, attention or working memory rather than reference memory, and the sensorimotor gating deficits induced by the NMDA receptor antagonist.