Reduction of blood eosinophil counts in eosinophilic chronic rhinosinusitis after surgery.

OBJECTIVE: This study aimed to predict eosinophilic chronic rhinosinusitis prognosis by investigating changes in the blood eosinophil count and other disease biomarkers after surgery. METHODS: Blood eosinophil numbers and serum interleukin-5 levels were measured in 22 eosinophilic chronic rhinosinusitis patients before and after functional endoscopic sinus surgery, and compared with equivalent measures in non-eosinophilic chronic rhinosinusitis patients and chronic rhinosinusitis without polyps patients. Differences between well-controlled eosinophilic chronic rhinosinusitis patients and those who experienced recurrence were also assessed. RESULTS: Blood eosinophil numbers and serum interleukin-5 level decreased after surgery in eosinophilic chronic rhinosinusitis patients. In this patient group, blood eosinophil counts before surgery were significantly higher in patients who experienced recurrence (825.7 ± 26.1 vs 443.9 ± 76.6 cells/µl, p < 0.05), and decreased significantly after surgery (825.7 ± 26.1 vs 76.7 ± 25.8 cells/µl, p < 0.05). CONCLUSION: Blood eosinophil numbers may reflect disease severity in eosinophilic chronic rhinosinusitis patients and their prognosis after surgery.

Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency.

It is commonly accepted that the presence of high amounts of maternal T cells excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We report a SCID patient with a novel mutation in the recombination activating gene (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS. Several assays, including representatives of specific T cell receptors (TCR), Vß families and TCR-γ rearrangements, were performed in order to understand more clearly the nature and origin of the patient's T cells. The patient had oligoclonal T cells which, based on the patient-mother human leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal origin. These cell populations were different in their numbers of regulatory T cells (T(reg)) and the diversity of TCR repertoires. This is the first description of the co-existence of large amounts of clonal expanded autologous and transplacental-acquired maternal T cells in RAG1-deficient SCID.

A novel macrolide/fluoroketolide, solithromycin (CEM-101), reverses corticosteroid insensitivity via phosphoinositide 3-kinase pathway inhibition.

BACKGROUND AND PURPOSE: Corticosteroid insensitivity is a major therapeutic problem for some inflammatory diseases including chronic obstructive pulmonary disease (COPD), and it is known to be induced by reduced histone deacetylase (HDAC)-2 activities via activation of the phosphoinositide 3-kinase (PI3K) pathway. The aim of this study is to evaluate effects of a novel macrolide/fluoroketolide, solithromycin (SOL, CEM-101), on corticosteroid sensitivity induced by oxidative stress. EXPERIMENTAL APPROACH: Corticosteroid sensitivity was determined by IC50/EC50 of dexamethasone (Dex) on TNF-α-induced CXCL8 production in U937 monocytic cell line and peripheral blood mononuclear cells (PBMC) from COPD patients. Activities of HDAC and protein phosphatase 2A (PP2A) were measured by fluorescence-based assay in cells exposed to hydrogen peroxide (H2O2). We also investigated steroid insensitive airway neutrophilia in cigarette smoke exposed mice in vivo. KEY RESULTS: SOL (10 µM) restored Dex sensitivity in PBMC from COPD patients, H2O2-treated U937 cells and phorbol 12-myristate 13-acetate-differentiated U937 cells. In addition, SOL restored HDAC activity with concomitant inhibition of Akt phosphorylation as surrogate marker of PI3K activation. The inhibition of Akt phosphorylation by SOL was due to increased PP2A phosphatase activity, which was reduced in COPD and oxidative stress model. Other known macrolides, such as eryhthromycin, clarithromycin and azithromycin, were significantly less effective in these responses. In cigarette smoke-exposed mice, SOL (100 mg kg(-1), po) showed significant but weak inhibition of neutrophilia, whereas Dex (10 mg kg(-1), p.o.) showed no such effect. However, a combination of SOL and Dex inhibited neutrophilia by over 50%. CONCLUSIONS AND IMPLICATIONS: SOL has potential as novel therapy for corticosteroid-insensitive diseases such as COPD.

Extranodal natural killer/T-cell lymphoma: a diagnostic dilemma.

BACKGROUND: The diagnosis of extranodal natural killer (NK)/T-cell lymphoma (NK/T-cell lymphoma) is often difficult and any delay in its diagnosis leads to a worsened prognosis. We analysed the factors that make the diagnosis of this type of tumour difficult. METHODOLOGY/PRINCIPAL: We retrospectively reviewed the medical records of 20 patients with NK/T-cell lymphoma treated in our department, and assessed the clinical features and laboratory findings of the cases. Moreover, we classified factors related to delays in diagnosing NK/T cell lymphoma as follows: (1) insufficient specimen size, (2) massive necrosis, (3) large number of inflammatory cells, and (4) poor atypia. We selected cases requiring two or more biopsies for correct diagnosis and checked which factors were the main cause of misdiagnosis. RESULTS: The average period required for a correct diagnosis was 12.8 months. The most frequent factor leading to diagnostic delay was inflammatory cell infiltration. Massive necrosis and poor atypia were also important factors in diagnostic delay. CONCLUSIONS: In cases with necrotic lesions of the nose or pharynx, the possibility of NK/T cell lymphoma should be explored and samples, of as large a size as possible, should be obtained together with EBER-ISH for pathological examination. Repeat biopsies should also be performed for diagnosis.

Ordered fullerene nanocylinders in large-diameter carbon nanotubes.

A new ordered fullerene phase encapsulated by large-diameter CNTs is systematically investigated by combining a growth technique by chemical vapour deposition, high-resolution transmission electron microscopy and molecular-dynamics simulations. In contrast to fullerenes in smaller (1-2 nm) diameter CNTs, where fullerenes are packed in linear or helical chains, fullerenes form a nanoscale cylinder in double-walled CNTs with diameters of ∼4 nm. The fullerenes were shown to form a nanocylinder with a side wall that resembled the (111) plane of solid C(60). This ordered phase is different from peapods or fullerene solids known so far, and a result of the interaction between the CNT wall and fullerenes. This finding will open up a new field of fullerene science.

Immunoregulatory defects of V alpha 24V+ beta 11+ NKT cells in development of Wegener's granulomatosis and relapsing polychondritis.

The frequency of either CD4(-)8(-) (double negative; DN) or CD4(+) V alpha 24(+)V beta 11(+) NKT cells, the expression of CD1d and the binding of CD1d-tetramer loaded with alpha-galactosylceramide (alpha-GalCer) to NKT cells were analysed in peripheral blood mononuclear cells (PBMCs) of patients with Wegener's granulomatosis (WG), relapsing polychondritis (RP) and healthy subjects (HS). DN and CD4(+) V alpha 24(+)V beta 11(+) NKT cells as well as CD1d-alpha-GalCer tetramer-positive NKT cells, were significantly decreased in number in both WG and RP patients compared to those from HS. When cytokine profiles were analysed in these PBMCs upon stimulation with phorbol ester and calcium ionophore, CD4(+) T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4(+) NKT cells from WG patients in remission showed a Th2 bias. These findings suggest that NKT cells (especially CD4(+) NKT cells) play a regulatory role in Th1 autoimmunity in patients with WG and RP. The reduction in NKT cell counts appears to be associated with the low responsiveness to alpha-GalCer. The dysfunction of NKT cells to recognize ligands such as alpha-GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.

Clinical study of adenoid cystic carcinoma of the head and neck.

OBJECTIVE: We examined prognostic factors and outcome of the primary treatment in patients with adenoid cystic carcinoma (ACC) of the head and neck. METHODS: Twenty patients with ACC of the head and neck who had been treated in our institution from 1985 to 1998 were enrolled in this study. Disease-specific survival rate was analyzed by the Kaplan-Mejer method, and the log-rank test was applied to compare the survival rates. RESULTS: The overall 5- and 10-year survival rates determined by Kaplan-Meier analysis were 81 and 57%, respectively. Patients with major salivary gland ACC obtained the best 10-year survival rate (83%), while those with paranasal sinus ACC had the worst survival rate (33%). Predominance of the solid component on pathological examination might indicate a worse prognosis. Our study revealed that postoperative radiotherapy could yield better control of the lesion focus. Chemotherapy failed in some patients and was not dramatically effective by itself. CONCLUSIONS: The long-term prognosis of ACC was poor. Long-term follow-up is necessary for better prognosis of patients treated with radical treatment regimens.

[Nasal allergies in Kushiro].

A clinical study of 107 patients with nasal allergies who were treated at Kushiro General Hospital between April 1998 and March 2000 was performed. Radioallergosorbent tests (RAST), X-rays, and nasal smears for the detection of eosinophilia were performed to obtain a diagnosis of nasal allergy. The patients (50 males, 57 females) ranged in age from 3 to 71 years. The RAST was positive for timothy in 22.4% of the patients, 14.0% for birch and 12.1% for mugwort. The most common pollinosis allergen in the Kushiro area was grass pollen. Other pollinosis allergens were birch pollen and mugwort pollen. We measured the daily count of dispersed birch pollen and timothy pollen in Kushiro and Sapporo. Birch pollen and timothy pollen was dispersed earlier in Kushiro than in Sapporo. Nasal allergies in the Kushiro area appear to be related to local characteristics, such as climate and geographical features.

Mechanisms of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery.

The effects of hydrogen peroxide were studied on isolated rabbit mesenteric small artery; rabbit superior mesenteric artery and mouse aorta were also studied as reference tissues. For mesenteric small artery, hydrogen peroxide (1 to 100 microM) relaxed a norepinephrine-stimulated artery in a concentration-dependent manner. The relaxation was not significantly affected by removal of the endothelium and was less pronounced in arteries contracted with high-KCl solution plus norepinephrine than in those contracted with norepinephrine alone. The relaxation response to hydrogen peroxide was increased by isobutylmethylxanthine and zaprinast, inhibited by diclofenac, methylene blue and dithiothreitol and unaffected by atropine, tetraethylammonium, superoxide dismutase, deferoxamine, dimethyl sulfoxide or the Rp stereoisomer of adenosine cyclic monophosphothioate. Hydrogen peroxide shifted concentration-contractile response curves for norepinephrine to the right and downwards. Norepinephrine and caffeine elicited a transient, phasic contraction of the mesenteric small artery exposed for 0.5, 1 and 2 min to a Ca2+-free solution. Hydrogen peroxide inhibited the norepinephrine-induced contraction, and to a lesser extent the caffeine-induced contraction, and verapamil did not alter the contraction to norepinephrine. These pharmacological properties of hydrogen peroxide were similar to those of 8-bromo cGMP; 8-bromo cGMP inhibited more potently the norepinephrine-induced than the KCl-induced contraction and the contraction elicited by norepinephrine in Ca2+-free solution. The present results suggest that hydrogen peroxide induces endothelium-independent relaxation of the rabbit mesenteric small artery precontracted with norepinephrine. The effects of hydrogen peroxide may be at least in part mediated by cGMP and cyclooxygenase products in the vascular smooth muscles now used.

Platelet size and function in septic rats: changes in the adenylate pool.

Cecal ligation and puncture (CLP) were performed in rats. After 4 hr (early sepsis) and 16 hr (late sepsis), platelet morphology and function were studied. At 16 hr, platelet counts for the CLP group were significantly lower than for the sham-operated control group. Low maximum aggregation rates (MAR) and decreased platelet counts were elicited in platelet-rich plasma with 4 M ADP and 2 micrograms/ml collagen. However, with platelet counts equalized, MAR for the CLP group increased significantly, especially after 16 hr. The platelet-large cell rate and platelet distribution width decreased temporarily at 4 hr, then rose significantly at 16 hr. No significant changes were observed in the mean platelet volume after 4 hr, but there were significant increases after 16 hr. Total adenine nucleotide (TAN) levels within the platelets rose significantly in the CLP group, suggesting the appearance during the late sepsis of large, heavy platelets or adenine nucleotide-rich platelets. The platelet adenylate pool was divided into granular and cytoplasmic fractions, respectively characterized by ADP and ATP increases. However, no septicemia-related differences were noted in the degree of binding between goat antirat fibrinogen and platelet surface glycoprotein IIb/IIIa complex. Internal environment changes in the platelets indicated that during septicemia hyperfunctional or hypersensitive platelets with a latent capacity for active aggregation and release appeared in the circulation. Hypercoagulability in septicemia involves activation of coagulation factors, stimulation of the coagulation cascade, volume changes accompanying increased platelet TAN content, and changes in AN distribution in the two pools. These findings significantly increase our understanding of the transition from the prethrombotic state to thrombosis in septicemia.

[Effects of the administration of urinary trypsin inhibitor on the morphology and function of platelets in the rat septic models].

Effects of urinary trypsin inhibitor (UTI) on the number, morphology and function of platelets under septic state were studied in rat models of cecal ligation and puncture (CLP). At formation of CLP, 5,000 U/kg/h of UTI was serially administered intraperitoneally and blood was sampled after 16 hours. Comparative study among sham-operation group, CLP group, and CLP + UTI group revealed: 1) inhibition of the platelets of platelet counts and appearance of large-sized, active platelets by UTI in the CLP + UTI group, 2) increase of platelet maximum aggregation rate (MAR) by ADP and increase of collagen in the CLP group, while inhibition in the CLP + UTI group and 3) by HPLC evaluation of adenine nucleotide in the platelet, increased levels of total ATP and ADP in the CLP group, particularly, increases of ATP in the metabolic pool and ADP in the granular pool. CLP + UTI group did not show these changes in the adenylate pool. UTI was thus considered to stabilize the platelet cycle in sepsis. Platelets under septic state might be hyperactive, and thrombosis is easy to occur. UTI administration might work for maintaining constancy of the platelet internal environment and improve septic state because adenine nucleotide level in the platelet did not change in the CLP + UTI group through changed in the CLP group.

Adrenal myelolipoma: a case report and review of the literature.

A case of a 73 year old man who was preoperatively diagnosed as possibly having myelolipoma is presented herein. Adrenal myelolipoma is an uncommon benign tumor of which only 74 foreign cases and 43 Japanese cases have been previously reported in the literature dealing with surgically removed myelolipomas. The most consistent complaint of the adrenal myelolipoma sufferer is abdominal pain, caused by hemorrhaging in the tumor, and many cases are associated with obesity, hypertension and/or diabetes mellitus. There is now an increasing number of such cases being diagnosed during abdominal scanning with ultrasonography or computerized tomography for unrelated problems, whereupon the myelolipoma is usually surgically resected. With the availability of modern scanning techniques and fine needle biopsy, however, it should be possible to adopt a more conservative approach to the management of asymptomatic adrenal myelolipoma. Nevertheless, symptomatic or large tumors, must be removed since there is a high risk of spontaneous hemorrhage.

"Spontaneous" pneumocephalus associated with aerobic bacteremia.

Three cases of "spontaneous" pneumocephalus suspected to have resulted from aerobic bacteremia caused by Enterobacter cloacae, Escherichia coli, and Klebsiella aerogenes are reported. In two cases, the E. cloacae and K. aerogenes were isolated from the cerebrospinal fluid. These cases were characterized by a rapid accumulation of air, without niveau, in the subarachnoid space and ventricles.

Determination of overt carnitine palmitoyltransferase by reversed-phase high-performance liquid chromatography.

A method for the determination of carnitine palmitoyltransferase I (CPT I; EC 2.3.1.19) in isolated rat liver mitochondria by reversed-phase high-performance liquid chromatography is described. Enzyme activity is assayed by direct determination of coenzyme A (CoA) released from palmitoyl-CoA within 60 min by a linear gradient system. CPT 1 in rat liver mitochondria can be assayed from only 30 micrograms of mitochondrial protein per millilitre of assay mixture. The changes in the kinetic parameters of CPT I, including Ki for malonyl-CoA, resulting from the fasting-feeding cycle are also discussed.

[Thrombotic thrombocytopenic purpura (TTP) associated with chromosomal aberration and treated with plasma exchange].

We reported a case of 69-year-old female presenting with clinically typical TTP which was treated with Ticlopidine and plasma exchanges four times in total and resulted in successful improvement of her clinical state. The first chromosomal analysis of lymphocytes in the peripheral blood of the patient revealed abnormal patterns of 45, XO/46, XX/47, XXX, the second, 45, XO/46, XX/47, XXX/47.XX, + 21. Measurement of FITC-labelled fibrinogen antibody against the fibrinogen combined with platelet glycoprotein GP IIb/IIIa complex using flow cytometry showed an apparently increased positive rate 76.2% for the platelet of the patient, compared with that of 31.9% for the control. From the comparative study of the platelet agglutination of the platelet rich plasma (PRP) derived from the citrated-added complete blood taken from the patient to whom Ticlopidine was given, added with adenosine-5'-diphosphate (ADP), collagen or acetyl glyceryl ether phosphoryl choline (AGEPC) as the reagents and that of normal control, it was shown that for AGEPC increased. Thus, increased reaction specific to AGEPC in addition to activated platelet was demonstrated in the present study.

Acute renal failure due to rhabdomyolysis associated with echovirus 9 infection: a case report and review of literature.

The occurrence of rhabdomyolysis and acute renal failure associated with viral infections is uncommon. We report a case of a 17-year-old female suffering from rhabdomyolysis caused by echovirus 9 in which the patient recovered after being treated for acute renal failure with hemodialysis. Among 42 cases of virus-induced rhabdomyolysis review in Japanese and English literatures, influenza virus is the most common cause of rhabdomyolysis, coxsackie virus tends to be next most common cause. Renal failure was recognized in 31 of the cases.

Altered hepatic fatty acid metabolism in endotoxicosis: effect of L-carnitine on survival.

The activities of palmitoyl-coenzyme A (CoA) synthetase, carnitine acetyltransferase (CAT), and carnitine palmitoyltransferase (CPT) and the levels of ketone bodies, reduced coenzyme A (CoASH), carnitine, and their esters, which are involved in fatty acid metabolism, in rat liver and plasma were measured after the administration of Escherichia coli lipopolysaccharide (LPS). We also studied the effect of L-carnitine treatment before LPS administration on survival and on hepatic fatty acid metabolism. The activities of CAT and CPT and the concentrations of ketone bodies, CoA, and carnitine derivatives (except for malonyl-CoA) declined in the liver after LPS administration. The activity of palmitoyl-CoA synthetase was changed little after LPS administration, and the level of hepatic malonyl-CoA increased significantly, suggesting that LPS causes activated fatty acids to undergo esterification and lipogenesis rather than oxidation. Treatment of rats with L-carnitine before LPS greatly increased the survival rate, but did not affect enzymes that metabolize fatty acids, CoA, or carnitine derivatives in the liver. Further studies are necessary to elucidate the mechanism of the effect of carnitine on post-LPS survival.

A case of ruptured duodenal varices and review of the literature.

The incidence of duodenal varices is exceedingly rare. A case of bleeding duodenal varices located in the third portion of the duodenum, secondary to idiopathic portal hypertension, which was successfully treated by surgery, is presented herein. Diagnosis was suspected at superior mesenteric angiography and was subsequently confirmed by endoscopy. A review of the literature reveals only 105 such cases in the world. While the duodenal bulb is the most common site of duodenal varices, the second portion of the duodenum appears to be the next most common site but duodenal varices in the other portions are extremely rare. From all of the possible causes of duodenal varices, liver cirrhosis remains the predominant etiological factor in 31 cases.