Gen Itoh

Primary lymphoma of the heart: Case report and literature review

Primary cardiac lymphoma (PCL) is a rare and usually fatal neoplasma. A case of PCL in a 78‐year‐old man who complained of exertional dyspnea and peripheral edema is presented. Echocardiography revealed a mass in the right atrium and a diagnosis of low‐grade B‐cell lymphoma was obtained with the surgically resected tumor. The lesion appeared to have originated in the right atrium and involved the right ventricle. The patient died of bronchopneumonia 8 months after the initial consultation. The present case and 39 patients with PCL reported between 1995 and 2002 were reviewed. Forty patients showed various and non‐specific symptoms such as dyspnea, edema, arrhythmia and pericardial effusion. Primary cardiac lymphoma occurred slightly more often in male patients (M : F = 23:17) and in the elderly in general (mean age, 67 years), with lesions found in the following locations, listed in order of frequency: right atrium, pericardium, right ventricle, left atrium, left ventricle, and other sites. Antemortem diagnosis was obtained in 37 of the 40 patients. Thirty‐seven cases were of B‐cell lineage and two cases were of T‐cell lineage. Complete remission was obtained in only 15 of the 40 patients. Although PCL antemortem diagnoses have been made in the majority of recent cases, the prognosis still remains poor.

The G12 family of heterotrimeric G proteins and Rho GTPase mediate Sonic hedgehog signalling

Sonic hedgehog (Shh) is a secreted morphogen crucial for cell fate decision, cellular proliferation, and patterning during vertebrate development. The intracellular Shh signalling is transduced by Smoothened (Smo), a seven‐transmembrane spanning protein that belongs to the G‐protein coupled receptor family. Among four families of Gα subunits, Gαi has been thought to be responsible for transducing Shh signalling, while several lines of evidence indicated that other signalling pathways may be involved. We found that the G12 family of heterotrimeric G proteins and the small GTPase RhoA are involved in Shh/Smo‐mediated cellular responses, including stimulation of target gene promoter and inhibition of neurite outgrowth of neuroblastoma cells. We also found that the G12/RhoA pathway is responsible for Smo‐induced nuclear import of GLI3 which is thought to transduce Shh signals to nucleus. Furthermore, misexpression of a G12‐specific GTPase‐activating protein in rat neural tubes leads to pertubation of motor neurone and interneurone development, mimicking the effects of decreased Shh signalling. These results show that Shh signalling is mediated in part by activating G12 family coupled signalling pathways. The participation of RhoA, a pivotal molecular switch in many signal transduction pathways, may help explain how Shh can trigger a variety of cellular responses.

Rat Small Intestinal Goblet Cell Kinetics in the Process of Restitution of Surface Epithelium Subjected to Ischemia-Reperfusion Injury

Repair of superficial damage to gastrointestinal mucosa occurs by a process called restitution. Goblet cells reside throughout the length of the intestine and are responsible for the production of mucus. However, a kinetic analysis of goblet cell dynamics of small intestine in restitution has hitherto not been reported. The aim of the present study was to investigate the role of goblet cells in the process of restitution of rat small intestine subjected to ischemia and ischemia–reperfusion injury, and therefore intestinal epithelium from rats subjected to both ischemia and ischemia–reperfusion was studied. Detachment of enterocytes was observed after 5-min of reperfusion. After 20–30 minutes of reperfusion, the denuded villous tips were covered with goblet cells. Within 75 min of reperfusion the epithelium restitution was complete. On the other hand, restitution was not observed in ischemia group. These data suggest that goblet cells may play an important role in restitution after ischemia–reperfusion injury.

Diversity of Restitution After Deoxycholic Acid-Induced Small Intestinal Mucosal Injury in the Rat

Repair of superficial damage to gastrointestinal mucosa occurs by a process called restitution, with epithelial integrity and continuity reestablished before cell proliferation occurs. The aim of the present study was to investigate the diversity of restitution in rat jejunum exposed to different concentrations of deoxycholic acid (DOC; 1.5–100 mmol/liter). Following a 30-min exposure, the intestine was allowed to recover for 15–330 minutes. DOC caused dose-dependent tissue destruction. Exfoliating epithelial cells were already observed after 5 min of exposure (1.5 mmol/liter), with simple sloughing off and resealing of the tips. Moderately affected epithelium (20 mmol/liter) demonstrated denudation of villous tips and then became covered with goblet cells. Severely affected epithelium (100 mmol/liter) also appeared to be replaced with goblet cells. These data suggest that the reversibility of mucosal damage induced by DOC is due to a variety of processes, which depend on the severity of the mucosal insult.

Cyclophosphamide-induced apoptosis induces phocomelia in the mouse

Abstract Phocomelia (absence of upper fore and/or hind limbs) was induced in mouse fetuses using cyclophosphamide. On day 11 of gestation, pregnant mice were injected intraperitoneally with 10 ml/kg of saline containing cyclophosphamide (CP) at a dosage of 20 mg/kg body weight. On day 18, the fetuses were removed by Caesarean section from dams given CP on day 11 and were examined for external anomalies. Of 22 fetuses from CP-treated dams, 13 were dead or absorbed, but the surviving 9 fetuses were found to have phocomelia with various other external anomalies. In order to examine the direct cytotoxic effect of CP on fetal limb buds, fetuses were removed at 8, 16, 24, and 48 h after CP administration on day 11, revealing the presence of frequent pyknotic nuclei and apoptotic bodies in hematoxylin and eosin (H & E) preparations. Cell-nuclei and apoptotic bodies were frequently observed by nick end-labeling in limb buds. Transmission electron microscopy demonstrated the typical changes of apoptosis. DNA extracted from the fetal limb buds submitted to CP was analysed by agarose gel electrophoresis, showing the ladder pattern characteristic of internucleosomal cleavage. These findings suggest that cyclophosphamide causes apoptosis in mouse fetal limb buds and that this process induces the external anomalies of phocomelia.

A case of primary malignant lymphoma of the liver.

SummaryPrimary lymphoma of the liver is extremely rare, and its preoperative or premortem diagnosis is still difficult. The author report here a case of primary malignant lymphoma of the liver diagnosed on a basis of ultrasonically guided biopsy of the tumor. A 51-year-old man was found to have a relatively large tumor in the right lobe of the liver as well as elevated serum LDH with abnormal isoenzyme pattern. Immunohistological studies of both biopsy and postmortem specimens of the tumor indicated T cell malignant lymphoma of the liver. The present case appears to be the second case of T cell origin of the disease.

Detection of purine nucleoside phosphorylase in paraffin sections by the immunoperoxidase method.

A method is described for immunohistochemical demonstration of purine nucleoside phosphorylase (PNP: EC 2.4.2.1) in paraffin sections from routine surgical histology specimens. A peroxidase-antiperoxidase (PAP) method was employed, using specific rabbit antiserum against human PNP, which was purified from postmature human erythrocytes. In human lymph nodes, intensive staining for PNP was observed in the vast majority of small lymphocytes in paracortical areas, in many small lymphocytes in medullary cords, and in a few small-to medium-sized lymphocytes in germinal centers. Small lymphocytes in the primary follicles and those in the mantle zones of secondary follicles were negative for PNP staining. Tingible body macrophages, lymphatic sinus cells, and most of the large cells in germinal centers did not stain with anti-human PNP (hPNP) antibody. Endothelial cells of small vessels in the cortex and plasma cells did not show any constant pattern of PNP staining intensity. Histochemistry revealed that the distribution pattern of PNP activity was quite similar to that demonstrated on paraffin sections by the PAP method.