Allogeneic cell stimulation enhances cytomegalovirus replication in the early period of primary infection in an experimental rat model.

BACKGROUND: Cytomegalovirus (CMV) diseases commonly occur in allograft recipients in the early post-transplant period. However, factors responsible for the high incidence of CMV diseases during this period are not yet fully defined. METHODS: Wistar-Furth (WF; RT-1(u)) rats were inoculated with 10(4) plaque-forming units (PFU) of rat CMV (RCMV) intraperitoneally, and then transplanted with allogeneic lungs from Dark Agouti (DA; RT-1avl) rats or stimulated with 10(7) mitomycin C-treated spleen cells from DA rats by daily sub-cutaneous injections for 2 weeks. No immunosuppressive agent was used. Naive WF rats and WF rats grafted with syngeneic lungs or cells were used as controls. The level of RCMV replication in rats was assessed by infectious virus titers in tissues. RESULTS: The virus titers in salivary glands of allogeneic and syngeneic lung graft recipients were significantly higher than in naive WF rats. The level of RCMV replication in rats stimulated with allogeneic spleen cells was significantly higher than in the syngeneic recipient rats: virus titers in the salivary gland of allogeneic and syngeneic recipients reached 4.61 +/- 0.33 and 4.00 +/- 0.37 log(10) PFU/g tissue, respectively, at 14 days post-infection (p = 0.015). The augmented viral replication in allogeneic recipients was confirmed by an increase in the number of RCMV antigen-positive macrophages present in tissue sections of the salivary gland. CONCLUSIONS: Acute lung allograft rejection and allogeneic spleen cell stimulation enhance CMV replication in the salivary gland of rats. Various responses to allogeneic antigens occurring in the process of acute allograft rejection could be risk factors for post-transplant CMV replication and infection.     

The translation and validation of the Japanese version of the patient assessment of constipation quality of life scale

Purpose

The aim of the present study was to conduct a psychometric evaluation of the patient assessment of constipation quality of life scale (PAC-QOL) in the Japanese language.

Methods

The PAC-QOL was translated into Japanese. After being linguistically validated, the Japanese version of the PAC-QOL was administered to a sample of 121 patients. Validation studies were conducted to evaluate the internal consistency reliability (Cronbach’s alpha), reproducibility [intraclass correlation coefficients (ICCs)], the convergent validity (correlated with the Short-Forum 36 Health Survey), the discriminant validity [correlated with the constipation scoring system (CSS)], the cross-sectional validity (analysis of variance models), and responsiveness (effect size) of the PAC-QOL scales.

Results

The internal consistency was good for all of the scales (Cronbach’s alpha coefficient >0.7) and reproducible (ICCs >0.7). The four scales of the PAC-QOL were significantly correlated with the Short-Forum 36 Health Survey (P < 0.01 except for the satisfaction subscale) and the CSS scores (P < 0.01 except for the satisfaction subscale). The PAC-QOL scale scores were significantly associated with constipation severity (P < 0.05). The effect size in patients reporting improvements in constipation over the treatment period was moderate to large, with a subscale effect size ranging from 0.69 to 1.18 and an overall scale effect size of 1.12. Similar findings were observed in the original validation study.

Conclusions

The linguistic and psychometric evaluation demonstrated the validity of the Japanese version of the PAC-QOL.

     

A hemodialysis patient with secondary hyperparathyroidism in whom primary parathyroid adenoma was resected 27 years previously

We report here a dialysis patient with secondary hyperparathyroidism who had a history of parathyroidectomy for primary hyperparathyroidism 27 years previously. The patient was a 48-year-old male. In 1974, he was diagnosed as having primary hyperparathyroidism and an adenoma was completely resected in the Department of Urology, Osaka University Hospital. In 1997, he started hemodialysis for chronic renal failure by diabetic nephropathy. Since his intact-PTH was high, we started intravenous vitamin-D pulse therapy, but intact-PTH did not decrease. We could not detect any parathyroid glands by ultrasonography and 201TlCl-99mTcO4-scintigraphy around the thyroid gland. Finally, chest-CT and 99mTc-MIBI scintigraphy revealed a ectopic parathyroid gland in the mediastine, and the ectopic parathyroid gland was successfully resected in July, 2001. In order to distinguish whether the resected ectopic parathyroid gland was due to primary adenoma or secondary hyperplasia, we used an immunohistochemical technique to examine the expression of PRAD1/cyclin D1, Ki67, and p27 and sequence analysis of the MEN1 gene. As a result, the labeling index (LI) of PRAD1/cyclin D1 was 4, LI of Ki67 was 36, and LI of p27 was 257. Moreover, germline-mutation and somatic-mutation of MEN1 gene was not detected. These findings suggested that the resected parathyroid gland was a nodular hyperplasia of secondary hyperparathyroidism. In conclusion, immunohistochemical findings of parathyroid tissue and sequence analysis of MEN1 gene could be useful for the differential diagnosis of primary adenoma and secondary hyperplasia.     

Differential FDG accumulation associated with GLUT-1 expression in a patient with lymphoma

We herein report a case of malignant lymphoma that showed differential FDG accumulation associated with the degree of glucose transporter 1 (GLUT-1) expression. For clinical staging purpose, FDG-PET was performed on a 47-year-old male who had been diagnosed to have malignant lymphoma, diffuse medium B-cell type. Although an X-ray CT showed multiple and bulky lymphadenopathy including bilateral submandibular, deep cervical, supraclavicular, axillar, hilar, mesenteric and paraaortic regions, FDG-PET showed a high accumulation only in the bilateral submandibular and deep cervical region. An immunohistochemical analysis demonstrated a high GLUT-1 expression in the right cervical lymph node, which showed a high FDG uptake. On the other hand, a bone marrow specimen with diffuse lymphoma cell involvement indicated showed no FDG accumulation and also revealed a negative GLUT-1 expression. This case suggests that the differential FDG accumulation shown by lesions is associated with the degree of GLUT-1 expression in patients with lymphoma.     

Comparison of a new heparin-coated dense membrane lung with nonheparin-coated dense membrane lung for prolonged extracorporeal lung assist in goats

Thrombosis and bleeding are major complications in cases of prolonged extracorporeal lung assist (ECLA) with an artificial-membrane lung. Antithrombogenic treatment of the artificial-membrane oxygenator and circuits is indispensable for safe ECLA. The efficacy of a new heparin-coated membrane lung with minimal systemic heparinization was evaluated for 7 days and compared with a nonheparin-coated membrane lung in goats. The animals were randomly assigned to either the heparin-coated membrane group (HM group, n = 5) or nonheparin-coated membrane group (NHM group, n = 5). Activated coagulation time (ACT) during ECLA was controlled to below 150 s in the HM group, and to near 200 s in the NHM group. All goats in the HM group were sustained on ECLA for 7 days, but two goats in the NHM group died on the 4th and 6th days, respectively. The mean systemic administration rate of heparin during ECLA was 22.4 +/- 4.4 U/kg/h in the HM group and 39.0 +/- 10.0 U/kg/h in the NHM group. There was a significant difference between the two groups (P < 0.05). The oxygen transfer rate, the Pco(2) difference, the perfusion resistance, and platelet counts showed no significant changes. There was no plasma leakage from the artificial lung. Although several clots were observed in the stagnant areas of the artificial lung, they did not lead to deterioration of the function of the artificial lung. The excellent antithrombogenicity, gas exchange ability, and durability of this new artificial lung with circuits might contribute to successful prolonged ECLA with minimal systemic heparinization.     

Cognitive inflexibility in Japanese adolescents and adults with autism spectrum disorders

AIM: To investigate executive function in Japanese adolescents and adults with autism spectrum disorders(ASD) compared to Japanese controls.METHODS: Thirty-three individuals with ASD and 33 controls participated. The ASD and control groups' demographic variables were matched for gender(male/female: 20/13 vs 20/13), age(26.1 ± 11.5 vs 26.8 ± 9.6), years of education(13.2 ± 2.9 vs 14.2 ± 1.9), full-scale intelligence quotient(IQ)(103.0 ± 16.7 vs 103.7 ± 14.7), performance IQ(96.2 ± 16.1 vs 97.8 ± 15.0), and verbal IQ(107.9 ± 16.3 vs 107.7 ± 14.4). Participants performed the Wisconsin Card Sorting Test(WCST), which assesses the executive processes involved in problem solving and cognitive flexibility, and the Continuous Performance Test(CPT), which assesses attention and impulsivity. Symptoms were assessed by the Autism-Spectrum Quotient Japanese version(AQ-J). First, we compared the scores of the WCST between the groups using a Mann-Whitney U-test and conducted an analysis of covariance for the variables with the scores of category archives and CPT scores as covariates. Second, we analyzed the correlation between the scores of the WCST and the AQ-J in the ASD group using Pearson's r.RESULTS: The total errors(TE) and the percentages of perseverative errors of the Milner type(%PEM) and Nelson type(%PEN) among the TE in the ASD group were significantly worse compared with the control group(ASD vs Control, respectively: TE: 16.0 ± 6.2 vs 12.6 ± 3.5, P = 0.012; %PEM: 11.7 ± 10.7 vs 6.6 ± 8.9, P = 0.037; %PEN: 20.1 ± 14.5 vs 8.7 ± 10.4, P = 0.0011). In contrast, no significant difference was observed between the two groups in the scores of categories achieved on the WCST or the CPT. An analysis of covariance revealed significant differences between the groups in the %PEN scores(P = 0.0062) but not in the TE or the %PEM scores. These results suggest that Japanese adolescents and adults with ASD have cognitive inflexibility. Furthermore, our results suggest that Japanese adolescents and adults with ASD may have difficulties using negative feedback because perseverative errors of the Nelson type indicate persistence in choosing the incorrect reaction. By contrast, there was no significant correlation between the WCST and AQ-J scores.CONCLUSION: We confirmed the presence of cognitive inflexibility in Japanese adolescents and adults with ASD. Our results also indicated that subjects with ASD may not use negative feedback effectively.     

Light/dark phase-dependent spontaneous activity is maintained in dopamine-deficient mice

Dopamine is important for motor control and involved in the regulation of circadian rhythm. We previously found that dopamine-deficient (DD) mice became hyperactive in a novel environment 72 h after the last injection of L-3,4-dihydroxyphenylalanine (L-DOPA) when dopamine was almost completely depleted. DD mice did not initially exhibit hyperactivity in their home cages, but the animals exhibited hyperactivity several hours after the last L-DOPA injection. The regulation of motor activity in a novel environment and in home cages may be different. A previous study reported that DD mice became active again approximately 24 h after the last L-DOPA injection. One speculation was that light/dark phase-dependent spontaneous activity might be maintained despite dopamine deficiency. The present study investigated whether spontaneous home cage activity is maintained in DD mice 24–43 h and 72–91 h after the last L-DOPA injection. Spontaneous activity was almost completely suppressed during the light phase of the light/dark cycle in DD mice 24 and 72 h after the last L-DOPA injection. After the dark phase began, DD mice became active 24 and 72 h after the last L-DOPA injection. DD mice exhibited a similar amount of locomotor activity as wildtype mice 24 h after the last L-DOPA injection. Although DD mice presented a decrease in activity 72 h after the last L-DOPA injection, they maintained dark phase-stimulated locomotor activation. Despite low levels of dopamine in DD mice, they exhibited feeding behavior that was similar to wildtype mice. Although grooming and rearing behavior significantly decreased, DD mice retained their ability to perform these activities. Haloperidol treatment significantly suppressed all of these behaviors in wildtype mice but not in DD mice. These results indicate that DD mice maintain some aspects of light/dark phase-dependent spontaneous activity despite dopamine depletion, suggesting that compensatory dopamine-independent mechanisms might play a role in the DD mouse phenotype.