Immunohistochemical analysis of steroidogenic enzymes in ovarian‐type stroma of pancreatic mucinous cystic neoplasms: Comparative study of subepithelial stromal cells in intraductal papillary mucinous neoplasms of the pancreas

Mucinous cystic neoplasms (MCNs) are generally defined as cyst‐forming epithelial neoplasms that arise in the pancreas and harbor characteristic ovarian‐type stroma beneath the epithelium. In this study, we compared the immunoreactivity of steroid‐related factors in these subepithelial stromal cells in MCNs to those in intraductal papillary mucinous neoplasms (IPMNs) to further characterize this unique MCN ovarian‐type stroma through evaluation of sex steroid biosynthesis. Twenty MCNs and twenty IPMNs were examined. Immunoreactivity of steroid hormone receptors, including estrogen receptor (ERα and ERβ), progesterone receptor (PR, PR‐A, and PR‐B), and androgen receptor (AR), was more frequently detected in MCN ovarian‐type stromal cells than in IPMN stromal cells (P < 0.01). The H‐scores (mean ± SD) of steroidogenic factor (SF)‐1 were also significantly higher in MCNs (112.3 ± 33.1) than in IPMNs (0.9 ± 1.2) (P < 0.01). The steroidogenic enzymes cytochrome P450 cholesterol side‐chain cleavage enzyme (P450scc), cytochrome P450 17 alpha‐hydroxylase (P450c17) and 3β‐hydroxysteroid dehydrogenase (3β‐HSD) showed immunoreactivity in 9/20 (45.0 %), 15/20 (75.0 %) and 13/20 (65.0 %), respectively, of ovarian‐type stroma from MCN cases. These results demonstrate that the ovarian‐type stroma of MCNs can express steroidogenic enzymes. Thus, the ovarian‐type stroma of MCNs can produce sex steroids that may also act on these cells.     

E and ID proteins regulate cell chirality and left–right asymmetric development in Drosophila

How left–right (LR) asymmetric forms in the animal body is a fundamental problem in Developmental Biology. Although the mechanisms for LR asymmetry are well studied in some species, they are still poorly understood in invertebrates. We previously showed that the intrinsic LR asymmetry of cells (designated as cell chirality) drives LR asymmetric development in the Drosophila embryonic hindgut, although the machinery of the cell chirality formation remains elusive. Here, we found that the Drosophila homologue of the Id gene, extra macrochaetae (emc), is required for the normal LR asymmetric morphogenesis of this organ. Id proteins, including Emc, are known to interact with and inhibit E‐box‐binding proteins (E proteins), such as Drosophila Daughterless (Da). We found that the suppression of da by wild‐type emc was essential for cell chirality formation and for normal LR asymmetric development of the embryonic hindgut. Myosin ID (MyoID), which encodes the Drosophila Myosin ID protein, is known to regulate cell chirality. We further showed that Emc‐Da regulates cell chirality formation, in which Emc functions upstream of or parallel to MyoID. Abnormal Id‐E protein regulation is involved in various human diseases. Our results suggest that defects in cell shape may contribute to the pathogenesis of such diseases.     

Clinical assessment of positron emission tomography for the diagnosis of local recurrence in colorectal cancer.

BACKGROUND: The clinical value of positron emission tomography (PET) for the diagnosis of local pelvic recurrence of colorectal cancer was evaluated. METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) of the pelvis were performed at regular intervals in 23 patients who had undergone resection for colorectal cancer. The 23 patients had a total of 25 lesions. PET images of the 25 lesions and of six primary lesions in patients with rectal cancer were obtained. A differential absorption ratio (DAR) was calculated in order to examine the accumulation of [18F]2-fluoro-2-deoxy-D-glucose (18FDG) on PET images. Histological diagnoses of the pelvic masses were obtained by CT-guided needle biopsy. RESULTS: On CT or MRI, a pelvic mass with a spicular shape (n = 1) was non-recurrent, whereas a nodular or lumpy shape indicated a locally recurrent lesion (n = 10). Masses with a nodulospicular shape (n = 12) did not correlate with the histological features. On PET, 15 of 16 histologically proven local recurrences were imaged positively. By setting a DAR of 2.8 as a cut-off value, local recurrences could be diagnosed with 100 per cent accuracy. CONCLUSION: PET is a clinically useful tool for the detection of local recurrence of colorectal cancer, particularly for distinguishing between recurrence and granulation tissues in the pelvic cavity.     

Eeffects of arteriovenous shunt on ventricular function in dog

Background: The bidirectional cavopulmonary shunt has been increasingly accepted as an interim step to the Fontan operation. However, the effect(s) of chronic volume overload on ventricular function are not yet well understood.Methods: Twelve mongrel dogs, with (chronic volume overload group), or without (control group) a femoral arteriovenous shunt created 8 weeks before the assessment, were subjected to a right heart bypass from the right atrium to the proximal pulmonary trunk. Nonpulsatile perfusion via the bypass was achieved using a centrifugal pump and cross-clamping of the pulmonary trunk. Left ventricular function was evaluated using the end-systolic elastance and the Doppler flow pattern on echocardiograms (epicardiac and transesophageal, simultaneously) during acute volume loading.Results: The left ventricular weight and the left ventricular weight/end-diastolic volume ratio showed no change from control values. The sum of the isovolumetric contraction time and the isovolumetric relaxation time divided by the ejection time remained constant during acute volume loading in the chronic volume overload group, while an increase was demonstrated in the control group. The chronic volume overload group showed a lower Ees (30.8 ± 16.4 mmHg/cm² vs. 107.6 ± 70.3 mmHg/cm², p=0.03) than the control group.Conclusions: The global ventricular performance changed with chronic adaptation to the arteriovenous shunt, and became resistant to acute volume loading. Left ventricular contractility under nonpulsatile pulmonary perfusion was impaired by chronic volume overload, which is deleterious to the Fontan operation.     

Effect of B7.1-transfected human colon cancer cells on the induction of autologous tumour-specific cytotoxic T cells

Background : The induction of tumour-specific immunity is important for advanced cancer therapy. There are many molecules, including costimulatory molecules, that have been identified as the activator for tumour-specific T cells. Methods : To induce autologous tumour-specific cytotoxic T lymphocytes (CTL) more effectively, we studied whether the expression of the B7 gene may render human colon cancer cells able to stimulate autologous peripheral blood mononuclear cells (PBMC) to become tumour-specific cytotoxic T cells. After the establishment of a B7.1 gene transfected tumour cell line, Cw2/B7.1, we first examined its stimulatory effect on autologous PBMC and subsequently, its effect on the induction of parental cell (Cw2)-specific CTL. Results : The results showed that Cw2/B7.1 had a more potent stimulatory effect on PBMC for the induction of both proliferation and cytotoxicity than Cw2. By adding a low dose of interleukin-2, Cw2/B7.1-activated killer cell activity was significantly increased. The specificity of Cw2/B7.1-activated killer cells was demonstrated by the absence of their cytotoxicity to either human lymphocyte antigen (HLA)-A33 identical (ORF) or HLA-non-identical (MT) allogenic colon cancer cell lines. Furthermore, such Cw2-specific cytotoxic activity was significantly reduced by the deletion of CD8⁺ cells but not CD4⁺ cells, indicating that these killer cells were mainly CD8⁺ T cells. Conclusions : Thus, our results demonstrate that, by using B7.1 gene-transfected tumour cell lines, we effectively induced autologous tumour-specific CTL. These results will provide us with new tools for adoptive immunotherapy for colon cancer patients. © 1999 Blackwell Science Asia Pty Ltd     

Detection of extrapancreatic nerve plexus invasion of pancreatic adenocarcinoma

Summary Background. Neural invasion is known to be one of the aggressive characteristics of pancreatic adenocarcinoma. However, there have been no systematic studies on intraoperative examination of neural invasion of pancreatic carcinomas after wide dissection of the retroperitoneum, paticularly at the surgical margin. Methods. We performed intraoperative immunostaining on the frozen sections of several excised plexus specimens, using peroxidase-labeled anti-cytokeratin 19 antibody in 17 cases of resectable pancreatic carcinoma. Postoperatively, we also tried to detect occult micrometastasis by direct sequencing of the K-ras gene in the same samples. Results. Intraoperative staining for cytokeratin 19 was positive in 4 of 17 (23.5%) cases. Patients with margin-positive neural invasion had significantly worse prognosis than patients who were margin negative (P<0.05). One patient had micrometastasis in the nerve plexus, revealed by K-ras mutation, whereas neither cytokeratin 19 staining nor postoperative pathological investigation detected involvement of the analyzed portion. In the four patients margin-positive for cytokeratin 19 staining, the diagnosis of neural invasion by cytokeratin 19 staining was in agreement with the K-ras gene analysis. Conclusion. Intraoperative staining for cytokeratin 19 is useful for detecting pancreatic cancer involvement of the neural plexus margin. The results can be also utilized as a prognostic indicator during the follow-up period.     

Case report of muscle cramp versus focal epilepsy]

We report here a boy suffering from muscle cramps in the right upper extremity. At 32 days of age, he developed purulent meningitis followed by paresis of the right upper extremity. From infancy he had intermittent episodes myoclonus-like involving the right hand. Since he also had true epileptic seizures with loss of consciousness, ocular deviation, and vomiting at 6 and 8 years of age, he was treated with anti-epileptic drugs as therapy for focal motor seizures. At 6 years of age, these episodes increased in frequency. The cramps spread from the right hand to involve the entire upper extremity with pain. At the age of 10, he was referred to Hirosaki University Hospital and was admitted. Using closed circuit television with continuous EEG and EMG monitoring we observed during his episodes repeated EMG abnormalities consisting of continuous discharges of polyphasic motor unit potentials, but no epileptic EEG discharges. We diagnosed these episodes as muscle cramp. His muscle cramps were controlled by medication with muscle relaxants and Chinese medicines. This case illustrates that the differential diagnosis between muscle cramps and epileptic seizures is important for proper treatment.     

Malignant hemangioendothelioma of the small intestine: Report of a case

(Received for publication on Feb. 18, 1998; accepted on Sept. 11, 1998)     

A solitary fibrous tumor in the perianal region with a 13-year follow-up: Report of a case

(Received for publication on June 5, 1998; accepted on Nov. 6, 1998)     

Protective involvement of nitric oxide in the liver injury induced by delayed-type hypersensitivity to picryl chloride

OBJECTIVE AND DESIGN: To investigate the role of nitric oxide (NO) in the liver injury induced by delayed-type hypersensitivity to picryl chloride (PCl-DTH). MATERIALS AND METHODS: Liver injury was induced in mice by PCl-DTH. NO production was examined using the Griess reagent. Isolated hepatocytes (HC) and nonparenchymal cells (NPC) were used. RESULTS: NO production in both serum and liver tissue reached a peak at 36 h after the elicitation of liver injury. The in vitro NO production was only observed by NPC or HC isolated at 24 h after the injury. Co-stimulation of IFN-gamma and TNF-alpha significantly triggered the HC and NPC isolated at 0 h to produce NO. As NO synthase inhibitors, Nomega-Nitro-L-Arginine exacerbated the liver injury in mice and NG-Monomethyl-L-Arginine enhanced the hepatotoxicity of IFN-gamma and TNF-alpha in vitro. In contrast, NO producer, S-nitroso-N-acetylpenicillamine dose-dependently inhibited the hepatotoxicity of NPC. CONCLUSIONS: NO may be produced by HC and NPC under the co-stimulation of IFN-gamma and TNF-alpha, and may play an important role for alleviating the liver injury.