First report of hepatobiliary Mycobacterium avium infection developing obstructive jaundice in a patient with neutralizing anti-interferon-gamma autoantibodies.

This study describes a patient who experienced hepatobiliary Mycobacterium avium infection associated with neutralizing anti-interferon gamma (IFN-γ) autoantibodies during treatment for disseminated M. avium disease. Hepatobiliary M. avium infection should be considered in jaundiced patients with neutralizing anti-IFN-γ autoantibodies, including those receiving antimycobacterial therapy for disseminated M. avium disease.

Serum lipid levels are positively associated with non-erosive reflux disease, but not with functional heartburn.

BACKGROUND: Metabolic syndrome and obesity are known risk factors for gastro-esophageal reflux disease (GERD), especially for erosive esophagitis. Although non-erosive reflux disease (NERD) is probably associated with obesity or other metabolic syndrome, there is little direct evidence to support this assertion. METHODS: Workers in Keio University who underwent a general health examination between September 2006 and August 2007 were enrolled. Reflux symptom questionnaires were administered and metabolic parameters were obtained. The severity of gastro-esophageal reflux (GER) was scored using a validated scale of videoesophagography. KEY RESULTS: Two hundred and eighty-three subjects (243 men and 40 women; mean age 49.8 +/- 6.9 years) with no radiographic evidence of erosive esophagitis were enrolled. The severity of GER was worse among men than among women, whereas the severity of reflux symptoms was worse among women. The severity of GER was associated with age and serum triglyceride levels in men, and with the serum low-density lipoprotein cholesterol levels in women. The severity of reflux symptoms, however, was not associated with metabolic parameters. There were more women than men with reflux symptoms but without GER ('presumed' functional heartburn group), compared with subjects with neither GER nor reflux symptoms. In men, the presence of both reflux symptoms and GER ('presumed' NERD group) was associated with the serum triglyceride levels. CONCLUSIONS & INFERENCES: While NERD is associated with serum lipid levels, functional heartburn is not. The prevalence of GER was greater among men; conversely, the prevalence of functional heartburn was greater among women.

Decreased gene expression of insulin signaling genes in insulin sensitive tissues of obese cats.

Type 2 diabetes mellitus (DM) animal models have provided ample opportunity for investigating pathogenesis, as well as to evaluate novel treatment and prevention options for the disease. Because the domestic cat shares a similar environment with humans, it is also confronted with many similar risk factors for diabetes, such as physical inactivity and obesity. Obesity is a significant risk factor for diabetes in cats, and as such, the domestic cat may serve as an ideal model for investigating obesity induced insulin resistance. This study determined changes in insulin signaling genes within insulin sensitive tissues of obese felines. Quantitative RT-PCR was performed to determine mRNA levels of three important insulin signaling genes which have been implicated with insulin resistance: insulin receptor substrate (IRS)-1, IRS-2, and phosphatidylinositol 3'-kinase (PI3-K) p85alpha. Obese cats had significantly lower IRS-2 and PI3-K p85alpha mRNA levels in liver and skeletal muscle as compared to control cats. This down regulation of insulin signaling genes in obese cats mirrors that of obese humans and rodents suffering from insulin resistance. Interestingly, preprandial blood tests indicated that our obese cats were no different from control cats with regards to glucose tolerance and insulin resistance, thus indicating that the obese cats used in our study had a moderate level of obesity. Therefore, insulin signaling gene alterations were occurring in insulin sensitive tissues of moderately obese felines before glucose intolerance was clinically evident. As such, the monitoring of key insulin signaling genes may have some important diagnostic value to determine the risk level and degree of obesity induced insulin resistance.

Kinetics and mechanism of the reaction of chlorine atoms with n-pentanal.

The kinetics and mechanism of the reaction Cl + CH3(CH2)3CHO was investigated using absolute (PLP-LIF) and relative rate techniques in 8 Torr of argon or 800-950 Torr of N2 at 295 +/- 2 K. The absolute rate experiments gave k[Cl+CH3(CH2)3CHO] = (2.31 +/- 0.35) x 10(-10) in 8 Torr of argon, while relative rate experiments gave k[Cl+CH3(CH2)3CHO] = (2.24 +/- 0.20) x 10(-10) cm3 molecule(-1) s(-1) in 800-950 Torr of N2. Additional relative rate experiments gave k[Cl+CH3(CH2)3C(O)Cl] = (8.74 +/- 1.38) x 10(-11) cm3 molecule-1 s(-1) in 700 Torr of N2. Smog chamber Fourier transform infrared (FTIR) techniques indicated that the acyl-forming channel accounts for 42 +/- 3% of the reaction. The results are discussed with respect to the literature data and the importance of long range (greater than or equal to two carbon atoms along the aliphatic chain) effects in determining the reactivity of organic molecules toward chlorine atoms.

Inhibition of angiogenesis by humulone, a bitter acid from beer hop.

On the basis of our previous finding that humulone, a bitter acid from beer hop extract, was a potent inhibitor of bone resorption and inhibited the catalytic activity of cyclooxygenase-2 (COX-2) and more potently the transcription of the COX-2 gene, we examined the effect of humulone on angiogenesis, using chick embryo chorioallantoic membranes (CAMs) and vascular endothelial and tumor cells. Humulone significantly prevented in vivo angiogenesis in CAM in a dose-dependent manner with an ED(50) of 1.5 microg/CAM. Humulone also inhibited in vitro tube formation of vascular endothelial cells. Moreover, it suppressed the proliferation of endothelial cells and the production of vascular endothelial growth factor (VEGF), an angiogenic growth factor, in endothelial and tumor cells. Thus, humulone is a potent angiogenic inhibitor, and may be a novel powerful tool for the therapy of various angiogenic diseases involving solid tumor growth and metastasis.

Structure-activity studies of analogues of blomhotin mediating contraction of rat fundus.

Blomhotin is a novel peptide (pGlu1-Gly2-Arg3-Pro4-Pro5-Gly6-Pro7-Pro8-Ile9-Pro10-Arg11) which has been isolated from the venom of Agkistrodon halys blomhoffii and exhibits contractile activity on rat stomach fundus. We carried out a structure-activity study of blomhotin and its related peptides, and the findings suggested that the N-terminal portion of blomhotin is mainly responsible for affinity for the blomhotin receptor, whereas the C-terminal portion of blomhotin, Pro-Ile-Pro-Arg, is responsible for complete activation of the blomhotin receptor in the rat stomach fundus. In particular, the amino acids at positions 9 and 11 of blomhotin appear to be essential for binding and intrinsic activity. Using knowledge gained from this structure-activity analysis, we have identified photoactive blomhotin analogues that have sufficient biological activity to probe the target molecule of blomhotin.

[Evaluation of MAST-26, newly developed system for the detection of IgE antibodies].

MAST-26 is a new allergy testing system which allows simultaneous determination of allergen-specific IgE antibody levels for 26 allergens using 200 microliters of patient serum. To evaluate the effectiveness of MAST-26 for the detection of allergen-specific IgE antibody, a total of 100 serum samples were collected from allergic patients at five facilities, and allergen-specific IgE antibody was measured by MAST-26. 14% of them were positive to > or = 10 allergens. If the patients had severe allergic symptoms, they were likely to show positive to many allergens. A good correlation was found between the results obtained by MAST-26 with those measured by CAP RAST and by intradermal skin test. It was concluded that MAST-26 is an effective screening method for the detection of allergen-specific IgE.

Amino acid sequence studies on cytolytic toxins from sea anemone Heteractis magnifica, Entacmaea quadricolor and Stichodactyla mertensii (Anthozoa).

The complete amino acid sequence of a cytolytic toxin, HmT, isolated from sea anemone Heteractis magnifica was determined. It is composed of 177 amino acid residues and lacks half-cystines. Partial N-terminal sequences of three other cytolysins from Entacmaea quadricolor (EnT) and Stichodactyla mertensii (SmT-1 and SmT-2) were also determined. Comparing these sequences with those of other sea anemone cytolysins, a high degree of homology was observed.

High prevalence of sensitization to cat allergen among Japanese children with asthma, living without cats.

BACKGROUND: Cat allergy is common among children with asthma. Many cat-allergic patients in Japan and elsewhere do not keep cats, but nonetheless become sensitized through environmental exposure to cat allergen. OBJECTIVE: To assess the frequency of cat allergy and cat-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibody responses in young Japanese patients with asthma in relation to self-reported cat exposure and Fel d 1 levels in dust samples. METHODS: Cat dander-specific IgE antibody was measured in sera from asthma patients using the CAP system. IgE and IgG antibody to Fel d 1 was measured by antigen binding radioimmunoassay and by chimeric enzyme immunoassay. Fel d 1 levels in dust samples from a subset of patients' homes were measured by monoclonal antibody-based enzyme immunoassay. RESULTS: Cat-specific IgE (CAP class>/=2) was found in sera from 70% of 44 patients who kept cats and 34% of 394 patients who had never kept cats. The prevalence of sensitization increased progressively to age 6 years (40%: positive), and then increased gradually to age 16 years (approximately 60%: positive) in patients who had never kept cats. There was an excellent correlation between cat CAP values and IgE levels to Fel d 1. The absolute amount of IgE antibody to Fel d 1 ranged from 0.01 to 15.6% of total IgE. Most patients who did not keep cats were exposed to Fel d 1 levels ranging from 0.07-8 microg/g dust. CONCLUSIONS: Sensitization to cat allergen is common among young asthmatic patients in Japan, even among patients who do not keep cats. Use of CAP and the chimeric enzyme-linked immunosorbent assay allows accurate diagnosis of cat allergy and quantification of specific IgE antibody levels.

[Food and food additives hypersensitivity in adult asthmatics. I. Skin scratch test with food allergens and food challenge in adult asthmatics].

OBJECTS: The aim of this study was to investigate in adult asthmatics, which kinds of food allergen can cause a positive reaction by skin scratch test and cause symptoms when administered as a food challenge. SUBJECTS AND METHOD: Three thousand one hundred and two adult asthmatic patients were submitted to skin scratch tests with housedust mite. Japanese cedar extracts and 33 types of food. Sixty one adult asthmatic patients with a history of immediate, adverse reactions after food ingestion underwent open food challenge. RESULT: Six hundred and twenty five of 3102 subjects (20.1%) had a positive test to one or more food allergens. The commonest food allergens were shrimp (27.7%), crab (27.7%), yeast (23.8%) and buckwheat (15.8%). The positive tests of shrimp, egg and cow's milk were highest in patients under 20 years and decreased with age, however the test rates of crab and soybean were not influenced by age. Positive food challenge responses occurred in 30/60 subjects (50%). The foods, which most of ten provoked a reaction, were buckwheat, shrimp, crab and bread. CONCLUSION: Skin scratch test results in adult asthmatics were different from those in atopic children where the commonest foods with positive tests were egg, cow's milk and soybean. Except for patients with a previous life-threatening reaction. Food allergy should be diagnosed by food challenge where a patient's history of adverse reaction to food, positive skin test and RAST strongly support specific food reactivity.

[Serum eosinophil cationic protein, urinary eosinophil protein X and urinary N-methylhistamine during acute asthma in children].

Serum eosinophil cationic protein (ECP), urinary eosinophil protein X (EPX) and urinary N-methylhistamine were investigated in 24 asthmatic children during acute asthma to determine the sequential variation in the parameters. Serum ECP levels and urinary EPX levels were high during acute asthma, and decreased gradually with improvement of acute asthma, however, these levels of eosinophil drived proteins were significantly higher than those in non-atopic children. There was no significant variation of urinary NMH levels. Significant inverse correlation was found between lung function and urinary EPX level. The present study suggests that serum ECP and urinary EPX may be useful for monitoring airway inflammation during acute asthma, and activation of eosinophils may persist after improvement of acute asthma.

[Slow-release theophylline for the treatment of asthmatic children].

The relative efficacy of theophylline therapy has been adequetely investigated for several decades. Benefits and risks from theophylline relate to serum concentration. Slow-release theophylline currently available in a variety of forms, including tablet, beaded capsule, granule, syrup and dry syrup. For children with chronic asthma requiring around-the-clock medication, slow-release formulations are more suited. Slow-release theophylline is likely to provide greater around-the-clock stabilization of hypersensitive airway and those given at night, provide effective control of nocturnal asthma symptoms. There is some variability between products and intrapatient variability on a day-to-day basis. Therefore therapeutic drug monitoring should be periodically conducted. There is increasing evidence for theophylline's anti-asthma properties, which include anti-inflammatory and immunomodulatory actions.

[Assay of specific anti-Chlamydia pneumoniae antibodies by ELISA method. 2. studies on clinical usefulness and serological diagnostic standards].

We measured anti-Chlamydia pneumoniae (C. pneumoniae) specific antibody titers by means of a newly-developed enzyme-linked immunosorbent assay (ELISA) method using an anti-C. pneumoniae specific antibody detection reagent. The clinical usefulness of this method was hereby evaluated. The IgG, IgA and IgM titers in 418 serum specimens obtained from patients with respiratory tract infections were measured by this new ELISA method, and the results were compared with the titers determined for the same specimens with the micro immunofluorescence (Micro-IF) method. The results showed good correlation coefficients for IgG, IgA and IgM. The two assay methods showed high agreement rates for positivity and for negativity. Specimens which did not yield the same results with the ELISA method and the Micro-IF method were subjected to analysis by the Western blot method, and the rates of agreement with the ELISA results were high. In addition, the child (0 approximately 15 yrs old; n = 122) and adult (16 approximately 90 yrs old; n = 133) cases were classified on the basis of being antigen-positive or antigen-negative at the initial examination, and their antibody-positive rates were determined. The adults showed no statistically significant differences in the antibody-positive rates for either IgG or IgA antibodies as a function of the pretreatment antigen status. However, the children showed statistically significant (p < 0.001) differences in the antibody-positive rates for both IgG and IgA antibodies as a function of the antigen status in the antigen-positive group compared with the rates in the antigen-negative group. Furthermore, the IgM-positive rates for the children were high in the antigen-positive group compared with the rates in the antigen-negative group, and the difference was statistically significant (p < 0.001). The IgM-positive rates in the adults were also significantly (p < 0.05) different between the antigen-positive group and the antigen-negative group. The Micro-IF method was applied to 34 specimens from antigen-positive patients, and 22 specimens were found to show an IgG titer of > or = 512 or an IgM titer of > or = 16. The diagnoses of these patients were acute respiratory disease in sixteen, pneumonia in four. Application of the ELISA-method to those 22 specimens showed all of them to exhibit IgG absorbance of > or = 0.6 and IgA absorbance of 0.2. The results described above indicate the clinical usefulness of our new ELISA method for the detection of antibodies specific for C. pneumoniae. The significance of this ELISA method for serological diagnosis of C. pneumoniae infections and the criteria for diagnosis of acute infections were also discussed.

[Clinical reliability of a new IgE detection system using chemiluminescent enzyme immunoassay named LUMIWARD immunoassay system].

The measurement of allergen-specific IgE antibodies and total IgE was performed with LUMIWARD immunoassay system (chemiluminescent enzyme immunoassay) using 406 serum samples obtained from patients with various allergic diseases and 81 serum samples from normal donors. These were collected by departments of internal medicine, pediatrics, dermatology and otorynolaryngology at eleven institutes in Japan. In addition to a comparative study with CAP RAST, skin tests were also performed to establish a clinical diagnosis. Simultaneous measurements were performed and an excellent correlation with CAP RAST was observed with a concordance rate of 92.6% and correlation coefficient of 0.922. The specificity determined by the normal serum samples was 96.4% for CAP RAST and 96.2% for LUMIWARD. The sensitivity determined by the samples, of which etiological allergens were identified clinically, was 84.8% for CAP RAST and 85.5% for LUMIWARD. Among them, the sensitivity of skin test was 91.8%. The concordance rate with clinical diagnosis was as high as 90.6% and 90.8% for CAP RAST and LUMIWARD. The normal upper limit of total IgE by cumulative 95% value was calculated to be 170 IU/ml for adult subjects. These results indicate the clinical usefulness of the LUMIWARD immunoassay system in evaluating IgE antibodies and total IgE.

[Diagnostic value of glass microfibre-based basophil histamine release test in food allergic children. Comparison with specific IgE antibody and skin scratch test].

We evaluated the diagnostic value of the glass microfibre-based histamine release test (HRT), which allows measurements to be performed using small amounts of whole blood, in 50 children with food allergy case histories. The patients were evaluated by radioallergosorbent tests (RAST), skin scratch tests (ST) and food challenge tests. Of the 50 patients, 39 had a confirmed clinical diagnosis of food allergy from food challenge tests and case histories, and were affected by a total of 60 positive allergens (egg 37, milk 11, soy beans 4, wheat 5, rice 3). The concordance, sensitivity, and specificity of HRT with the clinical diagnosis were 85.3%, 66.7% and 92.1%, those of RAST were 59.4%, 90.0% and 48.2%, and those of ST were 84.7%, 71.8% and 88.7%, respectively. The positive predictive values of HRT, RAST and ST were 75.5%, 38.8% and 66.7%. The false positive ratio of HRT (24.5%) was the lowest among all the tests. There was a significant correlation between HRT and RAST (r = 0.513, p < 0.001). However, the concordance of HRT with respect to RAST was 56.0%. The concordance and specificity of HRT in relation to the clinical diagnosis were higher than RAST and the same as ST. The sensitivity of RAST was higher than that of HRT. From these results, we concluded that RAST is good for the screening of allergens and that HRT is a useful diagnostic method for the confirmation of a clinical allergy.

Long-term survival in a patient with malignant carcinoid treated with high-dose octreotide.

Octreotide acetate, a long-acting somatostatin analogue, is effective in controlling and markedly reducing the symptoms of carcinoid crisis. We report a patient with carcinoid syndrome with prolonged survival for 4.5 years with high dose octreotide therapy and survived for 7.5 years after the first flushing, in spite of episodes of severe carcinoid crisis. Dose escalation was required in order to control carcinoid symptoms, and the final dosage was 5,950 micrograms/day. Although administration of such a high dosage of octreotide has never been reported before, we found that octreotide could be used at this dosage safely without inducing serious side effects, and probably prolonged the patient's survival. Our experience with this case indicates that octreotide acetate is an effective drug in controlling carcinoid crisis and prolonging survival without serious side effects.

A case of myelodysplastic syndrome progressing to acute myelocytic leukemia in which adult-onset Still's disease had occurred 6 years before.

A patient with adult-onset Still's disease who presented with myelodysplastic syndrome (MDS) after a course of 6 years is reported. To our knowledge, this is the first such reported case. The patient died of acute myelocytic leukemia. The possibility that cyclosporine contributed to the onset of MDS is discussed.

Treatment of disseminated intravascular coagulation with gabexate mesilate.

Gabexate mesilate (FOY) was used to treat 215 patients with disseminated intravascular coagulation (DIC) and 146 patients with a predisposition to DIC (pre-DIC). Sixty percent of DIC patients and 48% of pre-DIC patients exhibited pretreatment organ failure, which resolved after FOY treatment in 16% of DIC patients and 17% of pre-DIC patients. Seventy percent of DIC patients and 49% of pre-DIC patients had a pretreatment bleeding tendency that was ameliorated by FOY treatment in 32% of DIC patients and 30% of pre-DIC patients. Comparison of pretreatment and posttreatment hemostatic studies of the DIC patients revealed that platelet count and levels of fibrinogen degradation products (FDP), thrombin-antithrombin-III complex, and FDP-D-dimer decreased significantly; fibrinogen level increased markedly; and prothrombin time was prolonged. DIC scores were significantly lowered in both leukemic and nonleukemic patients from the third day of treatment with FOY. Among leukemic DIC patients, 59% showed complete remission (CR), 21% partial remission (PR), and 7% exacerbation of their condition; 46% of the nonleukemic DIC patients demonstrated CR, 17% PR, and 17% exacerbation. Of the leukemic pre-DIC patients, 59% showed improvement and 7% exacerbation, whereas 55% of the nonleukemic pre-DIC patients showed improvement and 27% exacerbation.