Cowden's disease diagnosed through mucocutaneous lesions and gastrointestinal polyposis with recurrent hematochezia, unrevealed by initial diagnosis

A 51-year-old man was admitted to our hospital because of hematochezia and painful keratotic plaques involving both hands. He had gastrointestinal polyposis, and a history of liver hemangiomas and thyroid tumor. Numerous papules on the face and papillomatosis on the oral mucosa were present. A diagnosis was made as a typical case of Cowden's disease according to the criteria proposed by Salem and Steck (J Am Acad Dermatol 8: 686, 1983). The patient was not correctly diagnosed initially in spite of typical manifestations of Cowden's disease, mainly due to his concomitant manifestations which occurred chronologically.     

Monocytes appearing repeatedly after chemotherapies had an identical rearrangement pattern of immunoglobulin with leukemic blasts in a patient with CD13+ acute lymphoblastic leukemia.

We recently encountered a patient with acute lymphoblastic leukemia (ALL) who showed temporal monocytosis of an unusually high cell count (5,000-30,000 monocytoid cells/microliter) five times after treatment with different chemotherapies. The leukemic cells expressed B-cell-associated antigens, CD19 and CD10, E-rosette receptor, CD2 and monocyte/myeloid antigen, CD13 simultaneously. They were peroxidase-negative. One week after the initiation of conventional chemotherapy for ALL, the leukemic blasts had disappeared. Alternatively, monocytoid cells appeared along with the recovery from nadir status. They showed several features of monocytes; they were weakly dot-positive for nonspecific esterase, reactive with CD14 and CD13 and Fc gamma-receptor-positive. Furthermore, they migrated into a fungally infected joint space. Features incompatible with normal monocytes were the absence of peroxidase reactivity, the expression of B-cell-associated antigens, CD19 and CD10 and E-rosette receptor, CD2. Southern blot hybridization analysis revealed an unexpected result that HindIII digested DNA from both leukemic blasts and monocytoid cells had the same rearranged band of IgH. Thus, an identical clonality of monocytoid cells, temporally appearing after chemotherapies and leukemic lymphoblasts, was determined in this patient with CD13+ ALL.     

Cloning and Characterization of a Unique Cytotoxic Protein Parasporin-5 Produced by Bacillus thuringiensis A1100 Strain

Parasporin is the cytocidal protein present in the parasporal inclusion of the non-insecticidal Bacillus thuringiensis strains, which has no hemolytic activity but has cytocidal activities, preferentially killing cancer cells. In this study, we characterized a cytocidal protein that belongs to this category, which was designated parasporin-5 (PS5). PS5 was purified from B. thuringiensis serovar tohokuensis strain A1100 based on its cytocidal activity against human leukemic T cells (MOLT-4). The 50% effective concentration (EC₅₀) of PS5 to MOLT-4 cells was approximately 0.075 μg/mL. PS5 was expressed as a 33.8-kDa inactive precursor protein and exhibited cytocidal activity only when degraded by protease at the C-terminal into smaller molecules of 29.8 kDa. Although PS5 showed no significant homology with other known parasporins, a Position Specific Iterative-Basic Local Alignment Search Tool (PSI-BLAST) search revealed that the protein showed slight homology to, not only some B. thuringiensis Cry toxins, but also to aerolysin-type β-pore-forming toxins (β-PFTs). The recombinant PS5 protein could be obtained as an active protein only when it was expressed in a precursor followed by processing with proteinase K. The cytotoxic activities of the protein against various mammalian cell lines were evaluated. PS5 showed strong cytocidal activity to seven of 18 mammalian cell lines tested, and low to no cytotoxicity to the others.     

In Vitro Analysis of Human Periodontal Microvascular Endothelial Cells

Background: Endothelial cells (ECs) participate in key aspects of vascular biology, such as maintenance of capillary permeability, initiation of coagulation, and regulation of inflammation. According to previous reports, ECs have revealed highly specific characteristics depending on the organs and tissues. However, some reports have described the characteristics of the capillaries formed by human periodontal ECs. Therefore, the aim of the present study is to examine the functional characteristics of the periodontal microvascular ECs in vitro. Methods: Human periodontal ligament‐endothelial cells (HPDL‐ECs) and human gingiva‐endothelial cells (HG‐ECs) were isolated by immunoprecipitation with magnetic beads conjugated to a monoclonal anti‐CD31 antibody. The isolated HPDL‐ECs and HG‐ECs were characterized to definitively demonstrate that these cell cultures represented pure ECs. Human umbilical‐vein ECs and human dermal microvascular ECs were used for comparison. These cells were compared according to the proliferation potential, the formation of capillary‐like tubes, the transendothelial electric resistance (TEER), and the expression of tight junction proteins. Results: HPDL‐ECs and HG‐ECs with characteristic cobblestone monolayer morphology were obtained, as determined by light microscopy at confluence. Furthermore, the HPDL‐ECs and HG‐ECs expressed the EC markers platelet endothelial cell adhesion molecule‐1 (also known as CD31), von Willebrand factor, and Ulex europaeus agglutinin 1, and the cells stained strongly positive for CD31 and CD309. In addition, the HPDL‐ECs and HG‐ECs were observed to form capillary‐like tubes, and they demonstrated uptake of acetylated low‐density lipoprotein. Functional analyses of the HPDL‐ECs and HG‐ECs showed that, compared to the control cells, tube formation persisted for only a brief period of time, and TEER was substantially reduced at confluence. Furthermore, the cells exhibited delocalization of zonula occludens‐1 and occludin at cell–cell contact sites. Conclusions: The present results provide new evidence that HPDL‐ECs and HG‐ECs have characteristics of fenestrated capillaries. Therefore, capillaries in human periodontal tissues have functional characteristics of fenestrated capillaries, which might be related to the onset and the progression of systemic diseases and inflammation.     

Higher Iron Intake Is Independently Associated with Obesity in Younger Japanese Type-2 Diabetes Mellitus Patients

We aimed to analyze the association between dietary iron intake and obesity assessed by BMI after adjustment for nutrient intake (macronutrients and fiber) and food groups. The study design was cross-sectional. Patients with type-2 diabetes (n = 1567; 63.1% males; mean age 62.3 ± 11.6 years) were included in the study. To assess diet, consumption of typical food groups was determined by a food frequency questionnaire. Obesity was defined as BMI ≥ 25 kg/m². We performed a binary regression analysis between quartiles of iron intake and obesity by quartiles of age group. A direct linear association was found for the highest quartile of iron intake and obesity in the younger age group of 30 to 54 years (OR = 3.641, 95% CI = 1.020–12.990; p trend = 0.011). Multivariate analysis using food groups as opposed to nutrients revealed a positive trend for obesity in the younger age group after adjusting for lifestyle factors, energy intake and bean and vegetable intake (p trend = 0.023). In all participants, an inverse association was observed before adjustment by vegetable intake (OR = 0.453, 95% CI = 0.300–0.684; p trend = 0.001). Higher iron intake was associated with obesity independent of macronutrient and fiber intake but only in the youngest quartile of age group examined.     

Conservative treatment of ruptured vertebrobasilar dissecting aneurysm

Ruptured vertebrobasilar dissecting aneurysm is usually treated surgically because rebleeding negatively affects outcome. However, the risk of rebleeding decreases markedly once several hours have passed from the initial bleeding. Moreover, surgery-related complications are not rare. We describe seven patients with ruptured vertebrobasilar dissecting aneurysm. To prevent rebleeding during the acute stage, we treated all seven patients conservatively with fentanyl instead of emergency surgery. During the follow-up period (mean 20 months), no patient suffered rebleeding. Conservative treatment with fentanyl administration may be a good option for management of ruptured vertebrobasilar dissecting aneurysm during the acute stage.     

Alterations of intrarenal adrenomedullin and its receptor system in heart failure rats

Calcitonin receptor-like receptor/receptor activity-modifying protein 2 (CRLR/RAMP2) and CRLR/RAMP3 complexes have been reported to be specific adrenomedullin (AM) receptors. In the present study, we evaluated the pathophysiological significance of renal AM and its receptor system in aortocaval shunt (ACS) rats. Renal AM levels were measured serially during 5 weeks after the operation. Renal gene expressions of AM, CRLR, RAMP2, and RAMP3 were measured at 2 weeks (decompensated phase) and 5 weeks (compensated phase) after the operation. Immunohistochemical localizations of renal AM were also evaluated. Furthermore, the relations between urinary sodium excretion (UNaV) and renal AM levels were evaluated. Renal AM levels were higher in ACS than in control animals only at 1, 2, and 3 weeks after the operation. At 2 weeks after the operation, renal AM mRNA expression was also higher in ACS than in control animals. CRLR, RAMP2, and RAMP3 mRNAs were expressed in the kidney, but there were no differences between the 2 groups. Immunohistochemistry revealed the positive AM immunostaining within the renal tubular cells, and it was more intense in ACS than in control animals. There were significant correlations between UNaV and renal AM levels. At 5 weeks after the operation, there were no differences in mRNA levels of AM, CRLR, RAMP2, and RAMP3 between the 2 groups. There was a significant correlation between UNaV and medullary AM levels. The present findings suggest that increased renal AM levels in decompensated heart failure, presumably due to increased AM production in renal tubules, in part, are involved in the regulation of sodium excretion.     

Effect of Taurine on Hemodiafiltration in Patients With Chronic Heart Failure

Taurine, an important factor in the living body, is essential for cardiovascular function and development and function of skeletal muscle, retina and central nervous system. In the present study, its effect on cardiovascular function was specifically taken into consideration. In hemodiafiltration (HDF) patients, the effect of taurine on patients with chronic heart failure (CHF), in whom dry weight was difficult to control, was evaluated. All patients who were subjected to regular HDF for 4 h three times per week at Joban hospital were included in this study. Patients with chronic heart failure, in whom dry weight was difficult to control (N = 4), were included in the evaluation of clinical status. X‐ray and echocardiography were determined before and after taurine treatment. Almost all patients were taking nitric acid, warfarin, anti‐platelet agents and vasopressors. Because vital signs were unstable in chronic heart failure, all cases withheld antihypertensive drugs during HDF. For unstable vital signs during HDF, pulmonary congestion was chronically recognized. After taurine was started, vital signs stabilized and lowering of dry weight was possible. In addition, X‐ray and cardiac diastolic failure on echocardiography improved. Taurine was effective for CHF patients on HDF in whom dry weight was difficult to control in spite of various medications.