Resectable carcinoma of the pancreatic head developing 7 years and 4 months after distal pancreatectomy for carcinoma of the pancreatic tail

A 67-year-old woman was referred with an abnormal finding on an abdominal echogram but presented with no symptoms; a pancreatic tail tumor was detected by ultrasonography. Biochemical examinations showed slight elevation of serum carcinoembryonic antigen level. The lesion was resected by tail and body pancreatectomy and her postoperative course was uneventful. Seven years and 4 months after the initial operation, however, her serum level of carbohydrate antigen 19-9 was found to be elevated, and a recurrence of pancreatic cancer was suspected. Examinations revealed a mass in the head of the remnant pancreas. The lesion was radically resected by total remnant pancreatectomy. Histological examinations showed that the initial tumor was a well differentiated tubular adenocarcinoma, while the second tumor was characterized as a moderately differentiated tubular adenocarcinoma. The surgical margins of the distal pancreatectomy specimen were free of atypical cells. Therefore, the position of the second lesion diminished the likelihood that it had developed by intrapancreatic metastasis. This suggests that the second carcinoma in the head of the pancreas may have been a second primary lesion. Received for publication on June 1, 1999; accepted on Sept. 20, 1999     

All-trans-retinoic Acid-dependent Inhibition of E-Cadherin-based Cell Adhesion with Concomitant Dephosphorylation of β-Catenin in Metastatic Human Renal Carcinoma Cells

We previously described an in vitro invasion assay model, using a monolayer of vascular endothelial cells grown on collagen gel, that mimics the metastatic abilities of the highly metastatic human renal carcinoma cell lines, MM-1,3 and 8 and their poorly metastatic counterparts, SN12C and Q-8. MM-1, 3 and 8 cells were observed to penetrate the monolayer of vascular endothelial cells and grew in a spreading or scattering manner with loose cell-cell contact on collagen gel or on vascular endothelial cells. SN12C and Cl-8 cells failed to penetrate and grew in a clustering manner with tight cell-cell contact. Treatment with all- trans -retinoic acid (ATRA) at non-toxic concentrations induced clustering or growth of MM-1, 3 and 8 cells on collagen gel or on vascular endothelial cells with tight cell-cell contact, and inhibited penetration. The clustering induced by ATRA was virtually blocked in the presence of anti-E cadherin antibody. E-Cadherin and β -catenin were each localized mainly at the cell-cell adherent junctions of colonizing cell populations that had been treated with ATRA. While the cellular levels of E-cadherin and β -catenin did not change significantly following ATRA treatment, the tyrosine residue of β -catenin was rapidly dephosphorylated. The concomitant administration of Na vanadate, an inhibitor of tyrosine dephosphorylase, inhibited both the ATRA-induced clustering and the dephosphorylation of β -catenin tyrosine. ATRA-induced clustering of MM-3 cells may be linked to the state of tyrosine phosphorylation of β -catenin.     

Observations of muscle plasma membrane undercoats in Duchenne and fukuyama muscula dystrophies

Muscle plasma membrane undercoats were investigated by conventional electron microscopy in both Duchenne muscular dystrophy (DMD) and Fukuyama congenital muscular dystrophy (FCMD). The densities of the plasma membrane undercoats were rarefied in the parts of the plasma membranes overlying the degenerating focus in both DMD and FCMD myofibers. The degree of rarefaction tended to be parallel to the degree of degeneration in the myofibers. It was hard to distinguish the undercoat densities of normal-looking myofibers of DMD and FCMD muscles from those of control myofibers from histochemically-normal muscles. On the other hand, the undercoats of regenerating myofibers in DMD and FCMD muscles were denser than normal.     

Reduced expression of aquaporin 4 in human muscles with amyotrophic lateral sclerosis and other neurogenic atrophies

Aquaporin 4 (AQP4) is a water channel protein that is widely distributed in human tissues. However, the precise functional role of AQP4 in skeletal muscle tissue has not yet been determined. Expression of AQP4 was reported to be reduced in muscle tissue from Duchenne muscular dystrophy patients. In the regenerating phase of skeletal muscle, AQP4 expression was reduced when nerve supply was not present. However, in diseased human muscles with neurogenic atrophy including amyotrophic lateral sclerosis, there has been no data on the changes in AQP4 expression. In the present study, we investigated the expression of AQP4 at mRNA and protein levels in human muscles with neurogenic atrophy. The mean level of AQP4 mRNA was significantly lower in muscles with neurogenic atrophy than that in muscles from normal controls. The myofiber surface immunostaining with anti-AQP4 antibody in muscles with neurogenic atrophy was reduced on the surface of scattered myofibers, small angulated myofibers, and myofibers in small- and large-group atrophy despite the presence of dystrophin. Based on the present findings, we conclude that the expression of AQP4 is affected by nerve supply and is down-regulated in human muscles with neurogenic atrophy.     

Mitochondrial DNA deletion of proximal tubules is the result of itai-itai disease

BACKGROUND: The pathogenesis of itai-itai disease continues to be controversial, although cadmium (Cd) poisoning which arises via polluted water and rice in Japan is likely involved. Until recently, however, a well-defined animal model for Cd intoxication was not available. An animal model for itai-itai disease was produced in rats by low-dose Cd treatment, intraperitoneally for a period of 70-80 weeks. Osteomalacia followed the renal damage. RESULTS: A gene deletion in the mitochondrial DNA was found in the mitochondria of the proximal tubule cells of rats with chronic Cd intoxication, as was shown by the increased smaller PCR product seen by gel electrophoresis in one DNA region, where ATPase and cytochrome oxidase genes are located. However, the PCR product was different from that seen with a gene deletion associated with aging: del4834bp. Renal damage from Cd intoxication initially caused mitochondrial dysfunction indicated by the disturbance in reabsorption in the proximal tubules and decreased amounts of ATP, ATPase, and cytochrome oxidase with gradually progressing tubular proteinuria, and, finally, chronic renal failure with tubulointerstitial damage throughout the renal cortex. These gave rise to osteomalacia, subsequently. CONCLUSION: We concluded that in Cd poisoning, a mitochondrial gene deletion in the mitochondria of the proximal tubule cells was the primary event for the pathogenesis of osteomalacia in itai-itai disease.     

Metastatic carcinoid tumor in the orbit

In 1991, a carcinoid tumor of the duodenum with metastasis in the regional lymph nodes was resected in a 39-year-old-man. A metastasis in the mediastinum was found and was resected in 1996. In 1999, a metastasis in the left lung was discovered and was excised. In 2001, he noticed right-sided diplopia, and a computed tomography (CT) scan disclosed a tumor of 2 cm diameter in the right orbit with infiltration to the frontal sinus. The tumor was resected, and was diagnosed metastatic carcinoid tumor. An orbital metastasis of carcinoid tumor is rare, and only about 30 cases have been reported in the English literature. The rarity metastasis of carcinoid tumors in the orbit prompted us to report this case.     

Reversible posterior leukoencephalopathy in a patient receiving cyclosporin therapy]

We reported a case of reversible posterior leukoencephalopathy syndrome (RPLS) that occurred during cyclosporin A (CyA) therapy for fulminant hepatitis. A 22-year-old man was given an intravenous drip of interferon-beta, metylprednisolone sodium succinate and CyA, and also received plasma exchange and hemodiafiltration. On the 7th day of the intravenous CyA therapy, in which its dose had been increased from 60 mg/day to 84 mg/day, he became somnolent and had headache, double vision, hallucination and then a generalized tonic-clonic seizure. The blood CyA concentration increased to a level as high as 455 ng/ml. Brain computed tomography (CT) scan without contrast medium revealed symmetric low-density areas in the bilateral occipital white matter and partly in the cortex. T2-weighted magnetic resonance imaging (MRI) showed an increased signal intensity, and single-photon emission CT using 99 mTc showed a hypoperfusion of cerebral blood flow in those areas. After CyA administration was changed to 100 mg/day orally to decrease its uptake in the blood, his consciousness and vision recovered within 4 weeks. Then abnormalities in MRI findings completely disappeared. On the basis of the clinical course and time-sequential change of serum CyA level in this patient, he was diagnosed as having RPLS caused by CyA therapy. Recently, the number of cases of RPLS has increased in the Western countries. However, there are few reports of RPLS after CyA therapy in Japan. From this case, we emphasize that careful following up the patient's neurological findings during CyA therapy is very important and that a cranial MRI is an essential tool for the diagnosis of RPLS.     

ACE inhibitors and its usefulness in the prevention of aspiration pneumonia in chronic cerebrovascular disease patients with asymptomatic swallowing dysfunction]

The double contrast pharyngogram by use of computed radiography (DCP-CR) has been found to be useful in detection of asymptomatic swallowing dysfunction. Following the DCP-CR examination, we investigated the incidence of aspiration pneumonia in 143 patients with chronic cerebrovascular disease (CVD) for 3 years and the effects of ACE inhibitors on the prevention of pneumonia. Aspiration pneumonia occurred in 29 out of 143 patients, and more frequently in the elderly chronic CVD patients with multiple brain lesions. Aspiration pneumonia was confirmed in 26 out of 85 patients (30.6%) with abnormal barium adhesion to the pharyngeal wall on the double contrast pharyngogram image by DCP-CR; whereas pneumonia occurred in 3 out of 58 patients (5.2%) with normal findings of DCP-CR pharyngogram. Among chronic CVD patients with abnormal findings of DCP-CR pharyngogram, the incidence of aspiration pneumonia was significantly lower in the patients treated with ACE inhibitors than in those treated with other antihypertensive agents or without antihypertensive agents (chi 2 value = 7.163, p < 0.05). Accordingly, ACE inhibitors may prevent the aspiration pneumonia and reduce the incidence of aspiration pneumonia in the chronic CVD patients with abnormal DCP-CR pharyngogram images.