Renal clearance of endogenous hippurate correlates with expression levels of renal organic anion transporters in uremic rats

Hippurate (HA) is a harmful uremic toxin that accumulates during chronic renal failure, and failure of the excretion system for uremic toxins is thought to be responsible. Recently, we reported that rat organic anion transporter 1 (rOat1) is the primary mediator of HA uptake in the kidney, and so now we have studied the pharmacokinetics and tissue distribution of HA after a single i.v. dose of HA to normal and 5/6 nephrectomized rats (5/6Nx rats). In control rats, the renal and biliary clearances of HA were 18.1 and 0.1 ml/min/kg, respectively. Plasma clearance decreased as dosage increased from 0.1 to 5 mg/kg, which suggests that renal tubular secretion is the primary route for elimination of HA. The plasma clearance of HA was significantly decreased in 5/6 Nx rats compared with normal rats. In 5/6 Nx rats, renal clearance of endogenous HA correlated more closely with clearance of p-aminohippurate than with that of creatinine. Protein expression of rOat1 and rOat3, assessed by Western blot analysis, was decreased in 5/6 Nx rats. Furthermore, in 5/6 Nx rats, the renal secretory clearance of endogenous HA correlated closely with protein expression of renal rOats. Thus, HA is primarily eliminated from the plasma via the kidney by active tubular secretion. The renal clearance of endogenous HA seems to be a useful indicator of changes in renal secretion that accompany the reduced levels of OAT protein in chronic renal failure.     

Challenging behavior of patients with frontal dysfunction managed successfully with behavioral intervention

Herein, we report on two clinical cases in which behavioral disturbances occurred due to frontal dysfunction. Both patients were treated successfully with behavioral intervention. In the first case, the patient's challenging behavior of repeatedly entering his wife's workplace and interrupting her work was reduced after the patient's wife changed her response to the behavior and her schedule prior to work to ensure that she spent time with him in the morning. In the second case, the patient's challenging behavior of urinating in the street was reduced by changing his walking route. The successful outcome in both cases suggests that behavioral intervention based on Antecedents, Behavior, and Consequences (ABC) analysis is useful in the management of behavioral disturbance due to frontal dysfunction.     

Differential inductions of small heat shock protein 27 and 1-Cys peroxiredoxin in reactive astrocytes in sulfatide-deficient mouse spinal cord

In myelinated fibers, various interactions among axons, oligodendrocytes, and astrocytes are present, particularly around the node of Ranvier. In the present study, we examined the protein composition of cerebroside sulfotransferase knockout (CST KO) mouse spinal cord by two-dimensional gel electrophoresis to examine the molecular changes resulting from the disruption of paranodal junctions in addition to the sulfatide-deficient condition. Interestingly, heat shock protein 27 (Hsp27) and 1-cys peroxiredoxin (1-Cys Prx) were both elevated in CST KO mice. Hsp27 was increased specifically in reactive astrocytes in the white matter, and the elevation was well correlated to the progression of neurologic symptoms. In contrast, 1-Cys Prx was elevated both in white and gray matter astrocytes in CST KO mice. These results suggest that astrocytes do not always respond stereotypically, as they display differences in their activation in these two regions. To determine whether these changes are specific to the sulfatide-deficient condition, spinal cords from CST KO mice and the hypomyelinating mutant shiverer mice were compared. The same distribution patterns of Hsp27 and 1-Cys Prx were found in reactive astrocytes in both CST KO and shiverer mice, suggesting that paranodal disruption with progressive nodal changes may underlie the similar reaction of white matter astrocytes. In contrast, CST KO and shiverer mice showed distinctly different localization patterns of connexin 43 and connexin 47, suggesting that intercellular communication between astrocytes and oligodendrocytes was different in these mutants. These results suggest that astrocytes may respond differentially to individual white matter abnormalities and may modulate specific axonal functions.     

Human papillomavirus type 16 variants in paired enrollment and follow-up cervical samples: implications for a proper understanding of type-specific persistent infections

Prospective studies of the persistence of human papillomavirus (HPV) variants are rare and typically small. We sequenced HPV-16 variants in longitudinal pairs of specimens from 86 women enrolled in the ASCUS-LSIL Triage Study. A change of variants was identified in 4 women (4.7% [95% confidence interval, 1.3%-11.5%]). Among women with intervening HPV results (n = 60), a variant switch occurred in 2 of 11 who had evidence of intervening negativity for HPV-16, compared with 1 of 49 who consistently tested positive (P = .11). These results suggest the possibility that rare misclassification of transient infections as persistent infections occurs in natural history studies of type-specific HPV infections.     

Coffee drinking and colorectal cancer and its subsites: A pooled analysis of 8 cohort studies in Japan

Coffee is a rich source of bioactive compounds that have potential anticarcinogenic effects. However, it remains unclear whether coffee drinking is associated with colorectal cancer. Also, despite different etiological factors involved in gut physiology, few studies have investigated this association by anatomical site of the lesion. To address these issues, this study examined the association between coffee drinking and colorectal cancer in a pooled analysis from 8 cohort studies conducted in Japan. Among 320,322 participants followed up for 4,503,274 person‐years, 6,711 incident colorectal cancer cases were identified. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using the random effects model. Coffee drinking was not materially associated with colorectal cancer risk in men or women (pooled HR 0.92, 95% CI 0.82–1.03 in men and pooled HR 0.90, 95% CI 0.76–1.07 in women). Analysis by subsite showed a lower risk of colon cancer among female drinkers of ≥3 cups coffee/day (pooled HR 0.80, 95% CI 0.64–0.99). There was no such association in men. Coffee drinking was not associated with risk of rectal cancer in men or women. Results were virtually the same among never smokers except for an increased risk of rectal cancer associated with frequent coffee consumption. Coffee drinking may be associated with lower risk of colon cancer in Japanese women.     

Primary cutaneous anaplastic large cell lymphoma occurring in an atopic dermatitis patient: a case report with review of the literature with emphasis on their association

Although the risk of malignant lymphoma in patients with atopic dermatitis (AD) remains controversial, an increased risk of malignant T-cell lymphoma in patients with AD has been reported. Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a relatively common distinct clinicopathological entity. However, occurrence of C-ALCL in patients with AD has been rarely reported. Herein, we describe the 5^th reported case of C-ALCL occurring in a patient with AD and review the clinicopathological features. A 30-year-old Japanese male with a long-standing history of AD presented with a gradually enlarged nodular lesion in the right abdominal wall, which had spontaneously regressed without therapy. Two years later, multiple nodular lesions appeared in his trunk, and swelling of multiple lymph nodes was also detected. Histopathological studies demonstrated diffuse proliferation of large-sized lymphocytes with large convoluted nuclei containing conspicuous nucleoli and relatively rich cytoplasm in the skin and lymph node. Immunohistochemically, these lymphocytes were positive for CD30, CD8, and MUM1, and negative for CD3, CD4, and ALK1. Accordingly, a diagnosis of primary C-ALCL was made. The patient died of disease after various courses of chemotherapy. Our clinicopathological review revealed that the prognosis of C-ALCL occurring in patients with AD is poor because two of 5 patients died of disease. Therefore, albeit extremely rare, AD patients with C-ALCL should be monitored closely, and additional clinicopathological studies are needed to clarify the pathogenesis of C-ALCL occurring in patients with AD.     

First Case Report of Fatal Sepsis Due to Campylobacter upsaliensis

We encountered a rare case of severe fatal infection in a 70-year-old woman due to Campylobacter upsaliensis, identified by PCR amplification and sequencing analysis of the 16S rRNA gene using DNA extracted from the isolates. To our knowledge, fatal sepsis due to this organism has never been described to date.