A case of acute hepatitis E associated with multidrug hypersensitivity and cytomegalovirus reactivation

A 65-year-old Japanese man was hospitalized because of acute hepatitis and severe cholestasis due to hepatitis E virus (HEV) infection combined with a drug reaction to a cold preparation. He died of disseminated intravascular coagulation and severe intestinal bleeding due to systemic cytomegalovirus reactivation following the development of severe eruptions with marked eosinophilia due to drug hypersensitivity to taurine and ursodeoxycholate preparations. The close interaction between viral infection or reactivation and drug hypersensitivity was considered as a pathophysiology in this case, which emphasizes the need for further study of the immunological mechanism of the interaction.     

Association of the GNAS1 gene variant with hypertension is dependent on alcohol consumption.

The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension.     

Traumatic degeneration of transected myelinated fibers of the mouse sciatic nerve.

Traumatic degeneration of myelinated fibers was studied by electron microscopy over 5 days following transection of mouse sciatic nerve. Special attention was paid to the mechanism which separates the degenerating part, while preserving the viable part of the axon. Immediately after transection, the opened end of the proximal stump revealed extensive subcellular changes including the disorganization of neurofilaments, and disruption of mitochondria and axonal endoplasmic reticulum (SER). Subsequently, vesicles of round and tubular profiles filled up the whole area of the stump end, and proximal to it appeared a neurofilament-predominant area characterized by randomly oriented neurofilaments and normally appearing mitochondria and SER. Characteristic membranous demarcations occurred in early periods at the border between the vesicle accumulation and the neurofilament-predominant areas, and later also within these areas. The demarcation membranes formed both by invagination of the surface plasma membrane and, probably, by fusion of the large vesicles. These became prominent with time, dividing the axoplasm into compartments of varying sizes, which gradually underwent degeneration and were liberated from the parent axon. Occurrence of autophagic vacuoles was characteristic of the degenerating portions of the parent axon. Thus, by the function of demarcation membranes, the parent axon to be preserved could remain membrane-bound, while the degenerating parts were shed off.     

Repeat operations in the management of clival chordomas: palliative surgery.

Some chordomas have a very poor prognosis because of their aggressive growth nature, but the efficacy of repeat operations for these cases has not been well documented. This report concerns 3 patients with aggressive chordoma of the clivus, who underwent operations 6 to 12 times over a period of 8 to 17 years because of symptomatic regrowth. Overall mean interval between repeat operations was 18 months with a range from 5 to 57 months and survival times were 9 to19 years after the first surgery. Main symptoms before each operation were diplopia and visual disturbance. Repeat palliative operations by intentional extradural debulking of the tumour to decompress offending neural structures, as well as maximal removal of the tumour, using appropriate skull base approaches, can mitigate progressive symptoms, and may result in better quality and some prolongation of life, although our patients gradually deteriorated neurologically throughout the clinical course.     

Production of monoclonal antibodies against human bladder cancer cells and application to immunohistochemical analysis of bladder cancer

Two hybridomas secreting two monoclonal antibodies IgG1 B1.4 and IgG2a B1.6 were obtained by immunizing BALB/c mice with human bladder cancer cell line EJ-1. In immunohistochemical staining of cryopreserved tissues, B1.4 reacted with 0 of 9 grade 1 TCC, 6 of 11 grade 2, all of 6 grade 3 and five metastatic specimens. The antigen recognized by B1.4 was not expressed by normal urothelial cells but were expressed by vascular endothelial cells and muscle of tunica media. The target antigen of B1.6 was expressed by normal urothelial cells and all grade of TCC. In this study, it was demonstrated that poorly differentiated bladder cancer and metastatic specimens of bladder cancer express a vascular carbohydrate antigen. Taking the escape mechanism of immune surveillance, into consideration, it is possible that the antigen recognized by B1.4 is an indicator of metastatic potential of bladder cancer.     

Experimental evaluation for tricuspid annular constriction with the model of tricuspid annular dilatation

We have obtained the good result about tricuspid annular constriction (TAC) for secondary tricuspid insufficiency. The purpose of this study is to investigate the effectiveness of TAC for the experimental model of tricuspid annular dilatation. First of all, tricuspid annular dilatation was made surgically in 8 mongrel dogs by placing 8 incisions to tricuspid annulus except septal cusp under the condition of heart-lung preparation. On clinical evaluation, septal annulus was kept to be intact in many cases compared with the two other areas. This experimental model of tricuspid annular dilatation was considered to be substituted to the clinical model of tricuspid annular dilatation. TAC suture was surrounded circumferentially around the dilated tricuspid annulus. And then, TAC suture was pulled out from the right atrial wall, and the circumferential length of tricuspid annulus was completely accommodated by pulling the TAC suture. The hemodynamic status was observed by right atrial pressure (V wave and mean) and right ventricular end-diastolic pressure (RVEDP). After heart resuscitation and gradual increase of preload, right atrial pressure was significantly elevated especially right atrial pressure (V wave) compared with control values. When 2 cm of circumferential length of tricuspid annulus on an average was constricted by shortening of TAC suture, right atrial pressure was significantly decreased, and then RVEDP tended to decrease. It was shown that TAC was an effective operative technique for the secondary tricuspid annular dilatation and tricuspid insufficiency from the standpoint of experimental aspect as well as clinical results.     

Surgical treatment of aortic arch aneurysm associated with the aberrant right subclavian artery

A 64-year-old man, who had an aneurysm of aortic arch associated with the aberrant right subclavian artery, was treated successfully. He was pointed out to have an aneurysm of aortic arch three years ago. Three years later angiograms and computed tomography revealed that it became larger compared with the initial finding. He underwent a replacement of the aortic arch using a woven Dacron graft under open distal method. Aberrant subclavian artery was not involved in the aneurysm. But because the left subclavian artery was involved in it, a woven Dacron graft was interposed between the ascending aorta and left subclavian artery. Postoperative course was uneventful and there were no complications.     

Three-dimensional MR vascular imaging of the spine using gadolinium-DTPA.

To investigate the fine vascular structures in the spinal and paraspinal region, the authors performed three-dimensional GRASS scanning after the administration of contrast material. The scan sequence was sagittal volume scan, TR/TE 100/16, with a flip angle of 45 degrees. First-order gradient moment nulling was employed. Four normal volunteers and 31 patients were studied. Using this technique, longitudinal anterior epidural veins and vertebral arteries were clearly identified. Paraspinal fine vessels of slow to moderate flow, including dilated anterior spinal artery, radiculo-medullary vein, and perimedullary coronal venous plexus, were demonstrated in pathological cases. In addition, with processing of the volume data set, phlebographic projection images of the ladder-shaped anterior epidural venous system could be generated. This method provided more detailed information on epidural and intradural vessels than conventional MR imaging.     

Successful Repair of the Right Atrial Isomerism, Double Outlet Right Ventricle, Cornmon Atrioventricular Canal, Pulmonary Stenosis, and Total Anomalous Pulmonary Venous Connection

A 6-year-old boy was successfully operated on for double outlet ventricle, common atrioventricular canal with severe valvular regurgitation, right atrial Isomerism, L-loop ventricles, total anomalous pulmonary venous connection, and pulmonary stenosis with hypoplastic left pulmonary artery. The Interventricular rerouting from the left ventricle to the ascending aorta was performed with a spiral patch, the lnteratrlal switching was performed by a Mustard patch, the common atrioventricular orifice was partitioned and valve repair was performed, and an 18-mm valved conduit was inserted between the right ventricle and the pulmonary artery. Although the patient had a small residual ventricular septal defect and pulmonary stenosls, the patient Is alive and well.     

The alloantigen-specific immunosuppressive activity of estradiol-chlorambucil conjugate (KM2210) and its beneficial effect on allogeneic bone marrow transplantation in mice.

KM2210, a conjugate of estradiol and chlorambucil (CBL), which was originally developed as an anti-breast cancer agent, inhibits proliferative response of human mononuclear cells to alloantigens in mixed lymphocyte culture in a dose-dependent manner, but has no effect on their response to phytohemagglutinin. Neither estradiol benzoate nor CBL alone showed these unique actions. The suppressive effect of KM2210 on MLC was abrogated by adding of anti-transforming growth factor-beta (TGF-beta) antibody to the culture, but was not affected by the addition of interleukin-2, suggesting that KM2210, unlike CBL, displays its actions via TGF-beta. In experimental allogeneic bone marrow transplantation using mice, daily oral administration of KM2210 (2 mg/kg/day) for 30 days posttransplant significantly inhibited the alloantigen-specific immune reactions. Furthermore, the survival rate of the KM2210-treated mice was significantly higher than that of the cyclosporine-treated (2 mg/kg/day, p.o.) mice, and no adverse effect of KM2210 on hematopoietic recovery was found. These results strongly suggest possible clinical benefits of KM2210 as a new immunosuppressive agent for the prevention and treatment of graft-versus-host disease and other allospecific immune reactions.