Survey of recognition and utilization of guidelines for the diagnosis and management of bronchial asthma in Japan

BACKGROUND: In Japan in 1993, the Japanese Society of Allergology (JSA) developed guidelines for diagnosis and management of asthma (JGL), which were based on the concept that asthma is a chronic inflammatory disorder of the airway. METHODS: This survey study was intended to investigate the recognition and utilization of JGL among physicians who had treated asthma. The survey comprised two methods: a quantitative mail survey and a qualitative door-to-door survey conducted by trained interviewers. RESULTS: In the mail survey, a total of 1028 physicians responded; 552 members of the JSA and 476 nonmembers. Ninety-four percent of JSA members were aware of adult asthma management guidelines, while 53% of nonmembers were aware of them. Although approximately half of the physicians, both members and nonmembers, found differences between the asthma management policies in JGL and their previous policies, most of them utilized JGL once they read it. In the qualitative door-to-door survey, 80-90% of physicians evaluated JGL as good after they read it. CONCLUSIONS: JGL was recognized and utilized by most JSA members, but only half of nonmember physicians were aware of JGL, although they utilized JGL after they read it. Further action to implement JGL among nonspecialist physicians is needed to improve management of asthma.     

IgE-mediated14C-serotonin release from passively sensitized rat mast cells: Comparative kinetic study with formaldehyde and ice-cold methods

The kinetics of IgE-mediated release of serotonin from passively sensitized rat mast cellsin vitro was studied by stopping¹⁴C-serotonin release with the application of formaldehyde fixative or ice-cold mast cell medium (MCM). Antigen dose-release curves of¹⁴C-serotonin and/or histamine were comparable when mediator release was terminated with either formaldehyde at a final concentration of 1% or ice-cold MCM 15 min after antigen challenge. However, the kinetic study of immunological mediator release stopped by formaldehyde showed that the addition of antigen resulted in a progressive increase of released¹⁴C-serotonin for 7 min, the release curve being sigmoidal, whereas the application of ice-cold MCM artificially enhanced¹⁴C-serotonin and histamine release in the first 2 min. The results suggest that stopping IgE-mediated release of¹⁴C-serotonin with formaldehyde is a simple, rapid and accurate method of studying the kinetics of mediator release from mast cells.     

Marked sequence diversity in the putative envelope proteins of hepatitis C viruses.

The nucleotide sequences of cDNAs (414 base pairs) encoding parts of putative envelope proteins (gp35 and gp70) of 40 isolates of hepatitis C virus (HCV-J) derived from 30 independent plasma or liver specimens from Japanese patients (13 with chronic hepatitis, 14 with hepatocellular carcinoma and 3 hemophiliacs who had received imported clotting factors), were analyzed using the polymerase chain reaction. Approximately 29-38% of the nucleotide sequences of the HCV-J isolates examined differed from those of isolates from the United States (HCV-US). Furthermore, 12-24% and 8-17% sequence diversities were found within the isolates of HCV-J and HCV-US, respectively. The diversities of the amino acid sequences were the same or greater than those of the nucleotide sequences. We confirmed that two hypervariable regions (HVR1 and HVR2) were present in this amplified region, as described in our previous report (Hijikata et al., 1991a) and we found that the HVR1 regions of HCV-J and HCV-US were 27 and 21 amino acids in length, respectively, and began from the N-terminal amino acid of gp70. HVR2 was found in HCV-J, but not in HCV-US isolates, in which the corresponding region of the genome was conserved. During the analysis, plural HCV genomes were found in 6 of 30 specimens. These plural HCV genomes in a single specimen were concluded to be derived from the same HCV ancestor, because of their relative low sequence diversities (about 10% in their nucleotide sequences).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neutral endopeptidase (EC 3.4.24.11) does not hydrolyze recombinant human interleukin-1 beta.

We have previously shown that neutral endopeptidase (NEP; EC 3.4.24.11) regulates neuropeptide-induced responses. Recently, Pierart et al. reported that NEP degraded purified interleukin-1 (IL-1) using thymocyte proliferation assay. Since IL-1 is an important cytokine in the immune response and inflammation, we have assessed whether NEP hydrolyzes recombinant human IL-1 beta using three assay systems (bioassay, immunoassay, and HPLC analysis). NEP on the NALM-6 cells (both intact cells and the solubilized plasma membrane fraction) efficiently hydrolyzed Met5-enkephalin and substance P. However, NEP did not significantly decrease the amount of rhIL-1 beta assessed by the growth inhibitory activity of a human melanoma, by the immunoassay, or by the direct analysis on HPLC. Therefore, we conclude that NEP does not significantly hydrolyze rhIL-1 beta. Our results suggest that, in contrast to the regulatory role of NEP in neuropeptide-induced responses, NEP is not a regulatory enzyme for IL-1-induced responses.     

AN AUTOPSY CASE OF METACHROMATIC LEUCODYSTROPHY

A case of metachromatic leucodystrophy was studied histologically and histochemically.
Metachromatic lipids were found in the liver, gallbladder, kidney, pancreatic islets and adrenal medulla, as well as in cerebral white matter. The main component of the stored lipids was histochemically proved to be sulfatide. However, besides sulfatide, cholesterol esters, fatty acids and a small amount of phosphatides were demonstrated in the enlarged cells in cerebral white matter. Histochemical characteristics of accumulated lipids in the metachromatic leucodystrophy were compared with those of various lipids in Tay-Sachs' disease, gargoylism, Gaucher's and Niemann-Pick's diseases. The acidic neutral red method was found effective for detecting sulfatide.     

General Pathology Of Kawasaki Disease

Systemic pathological alterations were studied in thirty-seven autopsied patients with Kawasaki disease. Systemic vasculitis was the most characteristic pathological finding and was present in all the patients. In addition to the vasculitis, there was a high incidence of inflammatory lesions in various organs and tissues: in the heart, endocarditis, myocarditis, and pericarditis; in the digestive system, stomatitis, sialoduct-adenitis, catarrhal enteritis, hepatitis, cholangitis, pancreatitis, and pancreas ductitis; in the respiratory system, bronchitis and segmental interstitial pneumonia; in the urinary system, focal interstitial nephritis, cystitis, and prostatitis; in the nervous system, aseptic leptomeningitis, choriomeningitis, ganglionitis, and neuritis; in the hematopoietic system, lymphadenitis, splenitis, and thymitis. Dermatitis, panniculitis or myositis were also observed in some patients. Therefore, Kawasaki disease is a systemic inflammatory disease which mainly affects the cardiovascular system. These systemic inflammatory lesions are considered to correspond to the variegated clinical manifestaitions. The relationship between Kawasaki disease and infantile polyarteritis nodosa (IPN) were discussed, based on the clinicopathological characteristics.     

Immunohistochemical differences between intracranial germinomas and their gonadal equivalents. An immunoperoxidase study of germ cell tumors with epithelial membrane antigen, cytokeratin, and vimentin

Twenty-six intracranial germ cell tumours (11 germinomas, 10 teratomas, 2 endodermal sinus tumours, 1 teratocarcinoma, and 2 undifferentiated embryonal carcinomas) and 26 gonadal germ cell tumours (13 testicular seminomas, 2 ovarian dysgerminomas, 9 ovarian teratomas, and 2 myometrial choriocarcinomas) were studied by immunoperoxidase with monoclonal antibodies (MAbs) against epithelial membrane antigen (EMA), cytokeratin, and vimentin. Typical tumour cells in three of the 11 germinomas (two of the latter being situated in the posterior fossa) expressed both EMA and cytokeratin, whereas those in the seminomas and dysgerminomas did not. In one seminoma, a few multinucleated giant cells expressed cytokeratin. In three of seven germinomas, vimentin-positive tumour cells were found, but all seminomas and dysgerminomas were negative. In the other forms of intracranial and gonadal germ cell tumours, epithelial and mesenchymal elements displayed the expected patterns of immunoreactivity to the respective determinants. The immunoperoxidase differences between the intracranial germinomas and their gonadal equivalents indicate that, in the former, early epithelial or mesenchymal differentiation of the primordial germ cells may be present. The findings draw attention to the heterogeneous cellular composition of these otherwise morphologically homogeneous-appearing tumours and, especially in the posterior fossa, to their transitional links to the immature teratomas.     

Immune responses of interferon gamma (IFN-gamma) knock out mice to repeated Haemaphysalis longicornis (Acari: Ixodidae) nymph infestations

To investigate the immunological mechanisms of acquired resistance to tick infestation, interferon gamma (IFN-gamma) deficient mice (IFN-gamma mice) were used to assess interleukin-4 (IL-4) and antibody production levels against tick salivary gland antigen on three successive infestations with Haemoaphysalis longicornis Neumann nymphs. The engorged body weight of the ticks decreased during the second and third infestations. Similar observations were noted in IFN-gamma+/+ mice. However, the engorged body weight of the ticks from IFN-gamma +/+ mice were considerably lower than those from IFN-gamma-/- mice. A marked increase in antibody production during the second and third infestations was observed indicating that IFN-gamma-/- mice could acquire immunological resistance against H. longicornis nymphs. Moreover, IL-4 levels were higher during the first and third infestations but decreased during the second infestation. IL-4 levels were significantly higher in IFN-gamma-/- mice than in IFN-gamma+/+ mice. We have shown here that the statistically significant high IL-4 levels observed in IFN-gamma-/- mice may be a result of type 2 helper cell (Th2) polarization. However, the apparently higher IL-4 levels during the first and third infestations and the notable decline during the second infestation suggest that other cytokines or factors in the host immune system may play a part in regulating IL-4 levels.     

Voxel-based morphometry of human brain with age and cerebrovascular risk factors

The objectives of this study were to evaluate the correlations of the volumes of the gray matter and white matter with age, and the correlations of the tissue probabilities of the gray matter and white matter with age and several cerebrovascular risk factors. We obtained magnetic resonance (MR) images of the brain and clinical information from 769 normal Japanese subjects. We processed the MR images automatically by correcting for inter-individual differences in brain size and shape, and by segmenting the MR images into the gray matter and white matter. Volumetry of the brain revealed a significant negative correlation between the gray matter volume and age, which was not observed between white matter volume and age. Voxel-based morphometry showed that age, systolic blood pressure, and alcohol drinking correlated with the regional tissue probabilities of the gray matter and white matter.