A cardiac allograft recipient with Bowen's disease on a finger and concurrent perianal bowenoid papulosis

We report a patient who developed Bowen's disease of the finger and bowenoid papulosis of the perianal area after cardiac transplantation. Human papillomavirus (HPV) type 16 only, not any skin-related or epidermodysplasia verruciformis-related types, was detected in both lesions by in situ hybridization and polymerase chain reaction. The same virus type was identified in both the tumor of the finger and the perianal area, which suggests contact transmission. HPV 16 has often been associated with malignant changes and may be at least one source of the malignancies that are more common in immunosuppressed patients. The presence of a potentially oncogenic type of the HPV in an immunosuppressed patient highlights the importance of regular follow-up of such patients.     

Inhibitory effects of angiotensin II receptor antagonists and leukotriene receptor antagonists on the transport of human organic anion transporter 4

Human organic anion transporter 4 (OAT4) is the only member of the OAT family that is expressed in the placenta and also expressed in kidney. Although OAT4 has been shown to transport certain organic anions as well as other members of the OAT family, fewer numbers of substrates have been identified for OAT4 compared with OAT1 and OAT3, suggesting that the substrate specificity of OAT4 is greater than other OAT members. However, the substrate specificity of OAT4 remains to be investigated in detail. The aim of this study was to examine the effects of various drugs on the OAT4-mediated transport of estrone-3-sulfate, a typical substrate of OAT4, by using human embryonic kidney cells stably transfected with OAT4 (HEK-OAT4). HEK-OAT4 cells exhibited concentration-dependent uptake of estrone-3-sulfate, with a K(m) value of 20.9+/-3.53 microM. Dehydroepiandrosterone sulfate and probenecid potently inhibited estrone-3-sulfate uptake. We also searched for the potential inhibitors of OAT4 and identified candesartan, candesartan cilexetil, losartan, losartan carboxyl (EXP3174) and valsartan as inhibitors of OAT4, with K(i) values of 88.9, 135.2, 24.8, 13.8 and 19.6 microM, respectively. The above angiotensin II receptor antagonists and leukotriene receptor antagonists share a common structural feature, that is the tetrazole group. Although pranlukast is devoid of anionic motifs other than the tetrazole group, it potently inhibited the OAT4-mediated uptake of estrone-3-sulfate, indicating that a tetrazole group may be one important structural feature in substrate recognition by OAT4.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2000). I. Susceptibility distribution

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of August 2000 and July 2001. Then, the susceptibilities of them to many kinds of antimicrobial agents were investigated. The number of them were 511 strains. The breakdown of these strains was Gram-positive bacteria as 29.0% and Gram-negative bacteria as 71.0%. Susceptibilities of these bacteria to antimicrobial agents were as follows; vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) showed strong activities against Enterococcus faecalis. No increase in low-susceptible strains of E. faecalis observed against these antimicrobial agents. VCM showed a strong activity against MRSA preventing growth of all strains with 1 microgram/ml. In addition, the activity of arbekacin (ABK) was strong with the MIC90 of 2 micrograms/ml against MRSA and prevented growth of all strains with 4 micrograms/ml. ABK showed a strong activity against Staphylococcus epidermidis preventing growth of all strains with 0.5 microgram/ml. ABPC, cefotiam (CTM) and cefozopran (CZOP) also showed a relatively strong activity against S. epidermidis (MIC90: 4 to 8 micrograms/ml). Against Escherichia coli, carbapenems showed high activities: meropenem (MEPM) prevented growth of all strains within 0.125 microgram/ml; IPM prevented growth of all strains with 0.25 microgram/ml. CZOP and CTM also showed strong activities against E. coli: MIC90 of CZOP was within 0.125 microgram/ml; MIC80 and MIC90 of CTM were 0.25 and 0.5 microgram/ml, respectively. Quinolone resistant E. coli was detected at frequency of 14.0%, which was significantly higher than that in the last year. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within 0.125 microgram/ml. Against Pseudomonas aeruginosa, almost drugs were not so active. The MIC90 of carbapenems and gentamicin (GM) were 16 micrograms/ml and those of all other drugs were more than 32 micrograms/ml. Against Serratia marcescens, the MIC90 of IPM and GM were the lowest value being 2 micrograms/ml, and that of MEPM was 4 micrograms/ml.     

Distributions of lesions in hanging suicide brains

We found a morphological similarity in the distribution of vascular lesions in five hanging suicide brains. The overall findings on the lesions remind us of the venous origin but not of the arterial origin of the blood supply. Morphometric evaluations did not reveal any valuable conclusion. The results of this pathological research may be of clinical importance for the treatment of hanging patients.     

Scavenger receptor type BI potentiates reverse cholesterol transport system by removing cholesterol ester from HDL

High-density lipoprotein (HDL) plays an important role in reverse cholesterol transport by removing accumulated cholesterol from extrahepatic tissues. Subsequently, cholesterol ester (CE) on HDL in humans is transported to apolipoprotein B-containing lipoproteins by cholesteryl ester transfer protein (CETP). CETP deficiency, which is common in the Japanese population, leads to a marked increase in HDL-cholesterol levels due to impaired CE transport from HDL to LDL. It has been reported that the HDL observed in CETP deficiency is an atherogenic lipoprotein, as it contains a large amount of CE. Scavenger receptor class B type I (SR-BI) has been found to be an authentic HDL receptor that mediates the selective uptake of HDL CE and the bi-directional transfer of free cholesterol between HDL and cells. In the present study, the interaction between SR-BI and CE-rich HDL from CETP-deficient patient was studied in order to evaluate the anti-atherosclerotic role of SR-BI in relation to CE uptake and reverse cholesterol transport. When CE-rich HDL was added to the medium of SR-BI-transfected CHO (SR-BI CHO) cells, more CE accumulated in SR-BI CHO cells compared to control HDL. In contrast, the amount of cholesterol efflux from SR-BI CHO cells into HDL was almost the same between the two HDLs. Therefore, when CE-rich HDL was added to the medium of SR-BI CHO cells, the intracellular CE content increased significantly. Moreover, the particle size of HDL in CETP-deficient patient decreased significantly when the HDL was added to the medium of SR-BI CHO cells, and this HDL showed an increment of CE efflux from foam cells. These results indicate that SR-BI reduces the cholesterol content and size of the CE-rich HDL from CETP deficiency, which ultimately activate reverse cholesterol transport system.     

Enhanced susceptibility of LDL to oxidative modification in a CTX patient:- role of chenodeoxycholic acid in xanthoma formation

Cerebrotendinous xanthomatosis (CTX) is a rare familial sterol storage disease, causing multiple xanthomas in tendons and the brain. The underlying biochemical defect is a lack of the hepatic mitochondrial cholesterol 27-hydroxylase involved in the normal biosynthesis of bile acid, resulting in reduced biosynthesis of chenodeoxycholic acid (CDCA). It has been reported that administration of CDCA to CTX patients improves neurological disorders and xanthomas of the Achilles tendon. The present study investigated the effect of CDCA on the mechanism of cholesterol accumulation in macrophages, the major cells in xanthoma. The LDL from the patients in this study was significantly more susceptible to oxidative modification than normal LDL, and supplement therapy with CDCA resulted in an improvement in the susceptibility to oxidative modification. In the incubation of CDCA with plasma, 13% of the CDCA added to serum was recovered in the LDL fraction. In addition, supplementation with CDCA enhanced cholesteryl ester transfer protein (CETP) activity and reduced high-density-lipoprotein cholesterol levels in the plasma. This evidence suggests that the multiple xanthomas observed in CTX may be induced by increased oxidized LDL and the low activity of CETP, both of which are caused by a lack of CDCA.     

Preoperative human-telomerase reverse transcriptase mRNA in peripheral blood and tumor recurrence in living-related liver transplantation for hepatocellular carcinoma

BACKGROUND/AIMS: In this study we evaluated the potential role of preoperative h-TERT mRNA expression in peripheral blood as a tool for predicting prognosis and tumor recurrence after living-related liver donor transplantation (LRLDT). METHODOLOGY: The study included patients with unresectable HCC who underwent LRLDT from July 1999 to May 2003. RESULTS: There was no significant difference between the survival curves of those patients who met the Milan criteria and those who did not. However, there was a statistically significant difference (p=0.032) between the survival curves of those patients with positive preoperative h-TERT mRNA expression, and those who either had an initially negative preoperative h-TERT mRNA or who converted from positive to negative after neoadjuvant immunochemotherapy. CONCLUSIONS: In conclusion, the presence or absence of h-TERT mRNA in the peripheral blood may be a useful criterion in evaluating HCC patients for transplantation, as well as a valuable method of assessing anti-tumor therapy and tumor relapse.     

Retrospective survey on the clinical features of non-Hodgkin lymphomas in Gunma Prefecture, Japan

We retrospectively investigated pathological types, clinical backgrounds, treatments and prognoses in 726 adult patients with newly diagnosed malignant lymphoma in Gunma Prefecture. They consisted of 679 patients with non-Hodgkin lymphoma (B-cell type, 603; T- and NK-cell type, 76) of which 376 patients had diffuse large B-cell lymphoma (DLBCL) and 47 patients with Hodgkin lymphoma. When comparing the prognosis of DLBCL between patients receiving rituximab (R-CHOP group; n=212) and not using rituximab (CHOP group; n=126), both 3-year overall survival (73.5% vs 61.7%, p=0.010) and 3-year progression-free survival (65.1% vs 45.8%, p<0.001) were statistically better in the R-CHOP group compared to the CHOP group. Our results suggest that more than half of patients were DLBCL and the rituximab-containing regimen results in an improved prognosis for DLBCL patients.     

In vitro performance and principles of anti-siphoning devices

Background

Anti-siphon devices (ASDs) of various working principles were developed to overcome overdrainage-related complications associated with ventriculoperitoneal shunting.

Objective

We aimed to provide comparative data on the pressure and flow characteristics of six different types of ASDs (gravity-assisted, membrane-controlled, and flow-regulated) in order to achieve a better understanding of these devices and their potential clinical application.

Methods

We analyzed three gravity-dependent ASDs (ShuntAssistant [SA], Miethke; Gravity Compensating Accessory [GCA], Integra; SiphonX [SX], Sophysa), two membrane-controlled ASDs (Anti-Siphon Device [IASD], Integra; Delta Chamber [DC], Medtronic), and one flow-regulated ASD (SiphonGuard [SG], Codman). Defined pressure conditions within a simulated shunt system were generated (differential pressure 10–80 cmH₂O), and the specific flow and pressure characteristics were measured. In addition, the gravity-dependent ASDs were measured in defined spatial positions (0–90°).

Results

The flow characteristics of the three gravity-assisted ASDs were largely dependent upon differential pressure and on their spatial position. All three devices were able to reduce the siphoning effect, but each to a different extent (flow at inflow pressure: 10 cmH₂O, siphoning -20 cmH₂O at 0°/90°: SA, 7.1?±?1.2*/2.3?±? 0.5* ml/min; GCA, 10.5?±?0.8/3.4?±?0.4* ml/min; SX, 9.5?±?1.2*/4.7?±?1.9* ml/min, compared to control, 11.1?±?0.4 ml/min [*p?2O/ siphoning -20cmH₂O: DC, 2.6?±?0.1/ 4?±?0.3* ml/min; IASD, 2.5?±?0.2/ 0.8?±?0.4* ml/min; SG, 0.8?±?0.2*/ 0.2?±?0.1* ml/min [*p?Conclusion The tested ASDs were able to control the siphoning effect within a simulated shunt system to differing degrees. Future comparative trials are needed to determine the type of device that is superior for clinical application.