Somatic Mutations of the PTEN/MMAC1 Gene in Fifteen Japanese Endometrial Cancers: Evidence for Inactivation of Both Alleles

Loss of heterozygosity (LOH) of chromosome 10q is observed in approximately 40% of endometrial cancers. Mutations in PTEN/MMAC1 , a gene recently isolated from the 10q23 region, are responsible for two dominantly inherited neoplastic syndromes, Cowden disease and Bannayan-Zonana syndrome. Somatic mutations of this gene have also been detected in sporadic cancers of the brain, prostate and breast. To investigate the potential role of this putative tumor suppressor gene in endometrial carcinogenesis as well, we examined 46 primary endometrial cancers for LOH at the 10q23 region, and for mutations in the entire coding region and exon-intron boundaries of the PTEN/MMAC1 gene. LOH was identified in half of the 38 informative cases, and subtle somatic mutations were detected in 15 tumors (33%). Our results suggest that of the genes studied so far in endometrial carcinomas, PTEN/MMAC1 is the most commonly mutated one, and that inactivation of both copies by allelic loss and/or mutation, a pattern that defines genes as "tumor suppressors,'contributes to tumorigenesis in endometrial cancers.     

The Effect of Total Blood Exchange with PHP Solution on Cardiac Xenotransplantation

Abstract: Prevention of hyperacute rejection is a difficult and unsolved problem in xenotransplantation. Natural antibodies and complement activation have been known to play an important role in the xenotransplantation between discordant species pairs. In the present study, total blood exchange (TBE) was performed with pyridox-alated-hemoglobin-polyoxyethylene conjugate (PHP) solution (Ajinomoto Co., Inc., Kawasaki, Japan) before cardiac xenotransplantation in order to remove the immunoglobulins and prolong xenograft survival time. Guinea pigs and rats were used as the discordant species combination for donor and recipient. Two groups were established: Group 1, untreated control (n = 8) and Group 2, TBT with PHP solution (n = 8). The exchange blood transfusion was carried out at the rate of 15–20 ml/h utilizing PHP solution using a blood pump. After the blood exchange was processed, hematocrit (Ht) levels dropped to 4 or 5%, and a cardiac xenotransplantation was performed within 24 h. The levels of serum IgA, IgM, and IgG were decreased to less than 25, 25, and 10% of the base line, respectively, after blood exchange. A mean xenograft survival time in Group 2 was prolonged to 472 ± 74 min and to 10.4 ± 1.8 min in Group 1 (p < 0.01). A titer of the anti-guinea pig lymphocytotoxic antibody in rat serum was decreased to almost nil. The data from this study suggest that total blood exchange with PHP solution may be useful in preoperative removal of xenograft antibodies in xenotransplantation.     

Barriers to Effective Case Management for Disabled Patients on Hemodialysis

The present study examined the performance level and its related factors on the process of case management for disabled patients on hemodialysis. Case management performance was evaluated at three stages: patient assessment, making a care plan, and monitoring/evaluation. Candidates for targeting the factors relating to performance included four dimensions: nursing care level, physical malfunction, cognitive malfunction, and barriers to service were used as patient factors; the period of case management for the patient and the knowledge of dialysis emerged as case manager factors; work load was included as an organizational factor; and community resources for these services and communication with surrounding persons were included as system factors. Self-administrated questionnaires were collected from 391 case managers of patients with hemodialysis certified long-term insurance. These were introduced by the dialysis facilities that a member of the Japanese Association of Dialysis Physicians belonged to. Case managers were asked questions about their management of each individual case. The results indicate, for example, that poor knowledge of dialysis is significantly related to poor patient assessment, inadequate development of a care plan, and lower levels of monitoring/evaluation. In addition, work overload and diabetic nephropathy as the primary kidney disease were also found to be significantly related to poor patient assessment. Increasing the opportunity for case managers to learn about dialysis may be needed for better case management performance in respect of the hemodialysis of disabled patients.     

Dose–response relationships of rabeprazole 5, 10, 20, and 40 mg once daily on suppression of gastric acid secretion through the night in healthy Japanese individuals with different CYP2C19 genotypes

Purpose  

This study was designed to investigate the antisecretory activity of rabeprazole administered once daily in doses of 5, 10, 20, and 40 mg and different cytochrome P450 2C19 (CYP2C19) genotypes on gastric pH in healthy individuals. Additional objectives were delineating the nighttime from the daytime effect and determining the relationships between the pharmacokinetics and pharmacodynamics of rabeprazole.     

Cause of early skeletal relapse after mandibular setback

The present study was undertaken to examine the factors that might be responsible for the skeletal relapse occurring during the period of intermaxillary fixation after mandibular setback osteotomy. Fifteen patients, treated for absolute mandibular prognathism by modified sagittal split ramus osteotomy and fixation by skeletal suspension wiring, were evaluated cephalometrically by reference to the degree of postsurgical superior shift of the gonial region of the distal segment as a parameter of relapse since such a shift was evident despite the use of wiring. It was found that the degree of inadvertent anteroposterior rotation of the proximal segment at surgery, rather than the extent and pattern of surgical repositioning of the distal segment, was significantly correlated with the degree of shift. This result emphasizes the justification of preserving the proximal segment in its exact original anatomic site, in addition to the use of skeletal fixation, to ensure predictable stability after mandibular setback osteotomy.     

Effects of Operating Conditions on Selectivity of a Plasma Fractionator in Double Filtration Plasmapheresis

Abstract: In a typical double filtration plasmapheresis treatment, plasma fractionation between albumin and some immunoglobulins associated with toxins is limited because none of the currently available plasma fractionators has a strict cutoff property for these proteins. Selectivity of immunoglobulins over albumin depends not only on the cutoff properties of the membrane but on the operating conditions such as the flow rate of the supplied plasma (Q_p ) and retained plasma to be discarded (Q_d ) in the plasma fractionator. We carried out an in vitro study using human plasma harvested by single plasma exchange treatments to assess the selectivity of a plasma fractionator, Evaflux 2A‐F (Kawasumi Laboratories, Inc., Tokyo, Japan), under various operating conditions. The results of rate‐constant filtration experiments showed that the concentrations in the feed tank and the sieving coefficient (SC) values of every protein were decreased slightly within 2 h after the start of the experiment because of membrane trapping, adsorption, and/or plugging. The time‐averaged SC value of albumin increased with flow rate ratio (Q_p /Q_d ) due to increasing filtration fraction (FF), but relative removal efficiency (m_D/m_P*) for albumin decreased with Q_p /Q_d due to decreasing Q_d . For immunoglobulins, on the other hand, the SC values were almost unchanged, and the m_D/m_P* values increased with Q_p /Q_d due to an increase in FF. Both increasing Q_p and decreasing Q_d are effective means of improving selectivity between these proteins in the plasma fractionator. Membrane fouling is, however, obvious beyond a Q_p /Q_d value that is thought to be a critical point. Operation should be conducted below the critical Q_p /Q_d value, which depends on the patient's plasma components and the cutoff property of the membrane.     

Antikeratin antibodies in sera of patients with connective tissue disease and liver disease

Sera from 93 patients with connective tissue disease, 36 rheumatoid arthritis, 41 systemic lupus erythematosus, 12 polymyositis/dermatomyositis and 4 systemic sclerosis and sera from 12 patients with liver disease, along with sera of 10 healthy subjects, were tested for antikeratin antibodies using enzyme-linked immunosorbent assay in which the wells were coated with human epidermal keratin. Values above the mean+SD of the 10 healthy subjects were found in 8.3% of rheumatoid arthritis, 29.3% of systemic lupus erythematosus, 33.3% of polymyositis/dermatomyositis, 50% of systemic sclerosis, 16.7% of liver disease patients, and 20% of healthy subjects. The results indicated a character of naturally occurring antibody of antikeratin antibodies in human sera.     

Prevention of progression of interstitial lung lesions by early combination therapy with corticosteroids and cyclosporine/cyclophosphamide in two patients with amyopathic dermatomyositis

Two patients with amyopathic dermatomyositis complicated by interstitial lung lesions were effectively treated with a combination of corticosteroids and cyclosporine and/or cyclophosphamide. A 48-year-old female patient was treated with pulse methylprednisolone and cyclosporine 2 months after onset of dermal symptoms. A 45-year-old male patient was treated with oral prednisolone and pulse cyclophosphamide 2 1/2 months after onset of dermal symptoms. Early evaluation of interstitial lung lesions and early extensive therapy may improve prognosis of interstitial lung lesions in patients with amyopathic dermatomyositis.     

Evaluation of blood access dysfunction based on a wavelet transform analysis of shunt murmurs

We investigated shunt murmurs based on wavelet transform analysis as a new method for assessing vascular access function. In the present study, in patients with venous stenosis near an arteriovenous fistula (A-V fistula), a sensor was placed at different positions around the stenosis and shunt murmur signals obtained using a measurement system were subjected to time–frequency analysis based on wavelet transforms. The shunt murmurs obtained from the stenotic region closely represented some features of murmurs that are often referred to as “high-pitch” murmurs in the clinical setting. In contrast, shunt murmurs obtained about 5 cm downstream of the stenotic region closely represented some features of murmurs that are often referred to as “low-pitch” murmurs in the clinical setting. Furthermore, with the aim of extending the lifespan of arteriovenous grafts (A-V grafts) by detecting and treating stenotic lesions before the A-V graft becomes occluded, we evaluated the possibility of utilizing the present shunt murmur analysis for monitoring stenosis in such A-V grafts. When shunt murmurs from patients with A-V grafts were analyzed, the results suggested that the blood flow through the venous anastomosis of the graft was the most turbulent. This present method whereby blood flow in an A-V fistula is assessed based on the frequency distribution on a time–frequency plane by wavelet transform analysis is advantageous because findings are not markedly affected by sensor attachment. Furthermore, because the sensor is attached using an adhesive collar, measurements can be taken over a short period of time before each dialysis session.