Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Two cases of mesenteric panniculitis]

Two patients with mesenteric panniculitis are presented. In the first patient, a provisional diagnosis of ileus was made, based on the clinical features and imaging data. Laparotomic findings showed that the ileum was bound tightly by a fibrous strip and dilated, with thickened and swollen mesentery. Incision of the fibrous strip was performed, and the clinical symptoms were improved. The second patient was strongly suspected to have mesenteric panniculitis, from characteristic features on abdominal computed tomography and barium enema. Conservative therapy was effective in this case. We emphasize the variety of clinical courses in mesenteric panniculitis, requiring selection of the most suitable treatment.     

A case of a small hepatoma with multicentric development in precirrhotic fibrosis

Multicentricity of hepatocellular carcinoma (HCC) is considered, especially in patients with liver cirrhosis. This paper describes an operative case of a male patient with probable multicentric development of HCC in precirrhotic fibrosis. The main tumors inside the capsule were completely necrotic due to transarterial embolization (TAE). Histologic examination disclosed discrete tiny nodules of HCC that were not detected grossly. They showed highly differentiated trabecular arrangements: Edmondson I. A scirrhous type was noted in the center of the tumors. At the borders of the tumors the carcinoma cells exhibited replacing growth patterns and it was thought that they developed multicentrically. Partial resection must be performed as extensively as possible in a case such as the present one.     

Preparation of two-drug composite microparticles to improve the dissolution of insoluble drug in water for use with a 4-fluid nozzle spray drier.

In this study, we used a novel 4-fluid nozzle spray drier to prepare composite microparticles of a water-insoluble drug, flurbiprofen (FP), and a water-soluble drug, sodium salicylate (SS), for the purpose of improving the water solubility of FP. An ethanol solution of FP and an aqueous SS solution were simultaneously introduced through different liquid passages in the 4-fluid nozzle spray drier and then spray-dried. Quantitative elemental analysis suggested that the FP/SS ratio in each composite microparticle was nearly the same as the formulation ratio. We also found that SS and FP exist in a low crystallinity state in the composite particles. Release of FP from dissolved composite microparticles was markedly improved because of an increase in the effective surface area following rapid dissolution of SS. This study shows that it is possible to prepare FP-SS composite microparticles using a 4-fluid nozzle spray drier in single process and that this can improve the ability of FP to dissolve in water.     

Accumulation of cyanide and thiocyanate in haemodialysis patients.

BACKGROUND: Cyanide is a toxic agent, and its detoxification product, thiocyanate, may be a major pathogenetic substance in uraemia. Recent studies examining the myeloperoxidase(MPO)/thiocyanate system have suggested a link between thiocyanate and atherosclerosis. However, inaccuracies in conventional assays for cyanide and thiocyanate have limited the understanding of their metabolism in haemodialysis (HD) patients. METHODS: We used high-performance liquid chromatography to measure cyanide in erythrocytes and thiocyanate in plasma in 43 HD patients and in a group of 46 healthy controls that included 15 current smokers. To clarify the metabolic conversion of cyanide to thiocyanate in uraemic patients, we also measured cysteine and sulfate. We then used stepwise regression analysis to analyse factors that determine erythrocyte cyanide and plasma thiocyanate. RESULTS: Mean cyanide and thiocyanate were significantly greater in HD patients than in non-smoking controls. However, cyanide was far below lethal concentrations in dialysis patients. Thiocyanate was six to seven times greater in HD patients than in non-smoking controls, and decreases in thiocyanate following dialysis were only 19.3+/-3.5%. Multiple regression analysis showed a positive correlation between cyanide and thiocyanate in controls, but a negative correlation in HD patients. In patients, an inverse relationship between thiocyanate and BUN was also observed. CONCLUSIONS: The elevation of thiocyanate in patients undergoing dialysis probably is secondary to both limited efficiency of HD and deranged metabolism of cyanide and thiocyanate. Because thiocyanate is a preferred substrate for MPO, it may play a role in uraemic complications including cardiovascular events.     

Interaction of CN-100, a novel non-steroidal anti-inflammatory drug, on biopolymers

Interaction of CN-100, a novel non-steroidal anti-inflammatory drug, with biopolymers were investigated. In collagen induced rat platelet aggregation, the inhibitory effect of CN-100 was almost equipotent as indomethacin (IM) but less potent than that of pranoprofen (PP). The effect of CN-100 on rat platelet aggregation induced by arachidonic acid (AA) was less potent than that of IM and PP. CN-100 inhibited rat platelet functions, serotonin release and malondialdehyde formation, induced by collagen more potently than those induced by AA. In heat-induced rat erythrocyte lysis and Ca2(+)-induced liposome aggregation, the inhibitory effect of CN-100 was less potent than IM but more than those of PP. CN-100 was inhibited with heat denaturation of BSA, and the effect was more potent than IM and PP. The metachromagy based on the binding of an azodye, HABA, to BSA was potentiated weakly by CN-100, but IM had no effect on it. CN-100 and IM increased the fluorescence of the binding of dansyl amide (site I probe) to BSA. These results support that there is considerable interaction between CN-100 and membrane protein, and this effect influences the membrane to increase its stability.     

Purification of rabbit, rat and mouse protein C with the use of monoclonal antibody to human protein C, PC01

Ca(++)-dependent monoclonal antibody specific to gamma-carboxyglutamic acid (Gla) domain of protein C was produced. It did not cross-react to the other vitamin K-dependent plasma proteins but to protein C of the other species. Using this monoclonal antibody, PC01, rabbit (170 micrograms), rat (60 micrograms) and mouse (40 micrograms) protein Cs were isolated from 100 ml of their plasma by affinity chromatography. All of these protein Cs were two chain form linked by disulfide bond as well as human protein C and activated by thrombin-thrombomodulin complex. Rat and mouse protein Cs showed similar characters to human protein C. On the other hand rabbit protein C had different M(r) of heavy and light chains and showed lower anticoagulant activity compared with human protein C.     

Bilateral subclavian steal associated with severe coarctation of the thoracic aorta and an aberrant right subclavian artery

A 10-year-old girl having bilateral subclavian steal associated with severe coarctation of the thoracic aorta and an aberrant right subclavian artery was found, on admission, to have no difference between upper and lower extremity blood pressure, but echocardiography revealed severe thoracic aorta coarctation and systolic blood pressure in the carotid arteries exceeding 200 mmHg estimated by Doppler ultrasonography. Magnetic resonance imaging and angiography demonstrated bilateral subclavian steal without esophageal compression. We reconstructed the aortic arch using the left subclavian artery and a reversed Blalock-Park procedure, then repaired the coarctation with a 14 mm woven double velor vascular graft. The girl was symptom-free following uncomplicated recovery from surgery. Doppler ultrasonography 2 weeks after surgery showed the pressure gradient across the aortic arch had decreased from 180 mmHg to 60 mmHg. This residual gradient at the anastomosis between the ascending aorta and left subclavian artery may improve as native vessels grow.     

Simultaneous repair of pectus excavatum and tetralogy of fallot: report of a case.

We report an 18-month-old boy with the association of pectus excavatum and tetralogy of Fallot (TOF). We successfully performed simultaneous pectus repair using sternal elevation without any prosthetic support and total correction of TOF after a prior modified Blalock-Taussig shunt. Retracting a divided costo-sternal complex with a rectus abdominal flap away from the operative field before the cardiac operation provided excellent surgical exposure. The modified Blalock-Taussig shunt prior to the combined repair prevented life-threatening hypoxic spells during dissection of the deformed sternum and costochondral cartilages before institution of cardiopulmonary bypass.     

Langerhans Cell Histiocytosis Presenting as a Varicelliform Eruption over the Entire Skin

A boy with skin eruptions resembling varicella and specific for Langerhans cell histiocytosis (LCH) is reported. At his initial visit when he was four months old, vesiculopustular lesions were present over the entire body; these had first appeared on the third day post partus. Histopathological, immunohistochemical, and electron microscopical examination confirmed the Langerhans cell phenotype and Birbeck granules in the responsible cells. He also had hydronephrosis, recurrent fever, and cutaneous bacterial infections. His parents refused further medical treatment and he died of diarrhea with cachexia about two years later. LCH may present diagnostic difficulties by manifesting as a skin eruption which resembles varicella.