Inhibition of passive cutaneous anaphylaxis-associated scratching behavior by mu-opioid receptor antagonists in ICR mice

BACKGROUND: Itching in humans is attenuated by mu-opioid receptor antagonists. ICR mice display increases in scratching behavior upon induction of IgE-mediated passive cutaneous anaphylaxis (PCA), or intradermal injection of compound 48/80 or histamine. METHODS: Cutaneous reactions were induced in ICR mice by IgE-mediated PCA, compound 48/80 and histamine, and the scratching behavior associated with the cutaneous reactions was evaluated. RESULTS: Naloxone and nalmefene reduced the incidence of scratching behavior associated with PCA. Naloxone also inhibited the induction of scratching behavior caused by compound 48/80 and histamine. Naloxone did not affect the increase in vascular permeability caused by PCA and injection of compound 48/80. CONCLUSION: Scratching behavior in mice may be induced by a sensation or a mechanism similar to itching in humans and should become a useful model for examining itching in humans.     

No evidence of PEG1/MEST gene mutations in Silver‐Russell syndrome patients

Silver‐Russell syndrome (SRS) is characterized by prenatal and postnatal growth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS. To clarify its biological function and role in SRS, we screened PEG1/MEST abnormalities in 15 SRS patients from various standpoints. In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (α and β) of PEG1/MEST were detected when they were compared with normal samples. Direct sequence analysis failed to detect any mutations in the PEG1/MEST α coding region, and there were no significant mutations in the 5′‐flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region. Differential methylation patterns of the CpG island for PEG1/MEST α were normally maintained and resulted in the same pattern as in the normal control, suggesting that there was no loss of imprinting. These findings suggest that PEG1/MEST can be excluded as a major determinant of SRS. © 2001 Wiley‐Liss, Inc.     

Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3

Prostaglandins, including PGD(2) and PGE(2), are produced during allergic reactions. Although PGD(2) is an important mediator of allergic responses, aspirin-like drugs that inhibit prostaglandin synthesis are generally ineffective in allergic disorders, suggesting that another prostaglandin-mediated pathway prevents the development of allergic reactions. Here we show that such a pathway may be mediated by PGE(2) acting at the prostaglandin E receptor EP3. Mice lacking EP3 developed allergic inflammation that was much more pronounced than that in wild-type mice or mice deficient in other prostaglandin E receptor subtypes. Conversely, an EP3-selective agonist suppressed the inflammation. This suppression was effective when the agonist was administered 3 h after antigen challenge and was associated with inhibition of allergy-related gene expression. Thus, the PGE(2)-EP3 pathway is an important negative modulator of allergic reactions.     

Comparison of various bone marrow fractions in the ability to participate in vascular remodeling after mechanical injury

In contrast to conventional assumption, recent reports propose the possibility that hematopoietic stem cells (HSCs) may have broader potential to differentiate into various cell types. Here, we tested the pluripotency of HSCs by comparing vascular lesions induced by mechanical injury after bone marrow reconstitution with total bone marrow (TBM) cells, c-Kit+ Sca-1+ Lin- (KSL) cells, or a single HSC cell (Tip-SP CD34-KSL cell, CD34- c-Kit+ Sca-1+ Lin- cell with the strongest dye-efflux activity) harboring green fluorescent protein (GFP). The lesions contained a significant number of GFP-positive cells in the TBM and KSL groups, whereas GFP-positive cells were rarely detected in the HSC group. These results suggest that transdifferentiation of a highly purified HSC seems to be a rare event, if it occurs at all, whereas bone marrow cells including the KSL fraction can give rise to vascular cells that substantially contribute to repair or lesion formation after mechanical injury.     

Effect of NZ-107, a newly synthesized pyridazinone derivative, on antigen-induced contraction of human bronchial strips and histamine release from human lung fragments or leukocytes.

The effects of a newly synthesized pyridazinone derivative, NZ-107, 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone, and two well-known antiasthmatic drugs, amlexanox (orally active disodium cromoglycate-like drug) and disodium cromoglycate (DSCG) on antigen-, histamine- and leukotriene C4 (LTC4)-induced constriction of isolated human tracheal muscle, and histamine release from human lung tissues and leukocytes were investigated in vitro. In some experiments, salbutamol was used as a reference drug. NZ-107 inhibited antigen-, histamine- and LTC4-induced contraction of tracheal muscle. Amlexanox and DSCG did not affect the contractile response of tracheal muscle caused by each stimulant. Salbutamol inhibited antigen-induced contraction of tracheal muscle. NZ-107, amlexanox, DSCG and salbutamol clearly inhibited the antigen-induced release of histamine and LTC4 from human lung tissue. The antigen-induced histamine release from atopic human leukocytes was inhibited by NZ-107 and amlexanox, but not by DSCG. Pretreatment with IL-3 did not alter antigen-induced contraction of tracheal muscle and histamine release from lung tissue, but antigen- or calcium ionophore A 23187-induced histamine release from leukocytes was clearly enhanced. Amlexanox inhibited the IL-3-induced enhancement of histamine release from leukocytes in the case of both stimuli, but NZ-107 and DSCG had no effect. These data suggest that NZ-107 has potent anti-allergic actions based on the inhibition of antigen-induced contraction of human tracheal muscle and mediator release from human lung tissue and leukocytes.     

Acellular pertussis vaccines in Japan: past, present and future

An antivaccine movement developed in Japan as a consequence of increasing numbers of adverse reactions to whole-cell pertussis vaccines in the mid-1970s. After two infants died within 24 h of the vaccination from 1974 to 1975, the Japanese government temporarily suspended vaccinations. Subsequently, the public and the government witnessed the re-emergence of whooping cough, with 41 deaths in 1979. This series of unfortunate events revealed to the public that the vaccine had, in fact, been beneficial. Furthermore, researchers and the Japanese government proceeded to develop safer pertussis vaccines. Japan now has the most experience worldwide with acellular pertussis vaccines, being the first country to have approved their use. This review describes the major events associated with the Japanese vaccination program. The Japanese experience should be valuable to other countries that are considering the development and use of such vaccines.     

Genetic variations in five genes involved in the excitement of cardiomyocytes

We provide here 29 genetic variations, including 28 novel ones, in five genes that are potentially involved in the excitement of cardiomyocytes: we found 4 in KCNA10, 2 in KCNK1, 8 in KCNK6, 11 in SLC18A1 (VMAT1), and 4 in SLC6A2 (norepinephrine transporter). We also examined their allelic frequencies in a Japanese population of long QT syndrome-affected and nonaffected individuals. These data would be useful for genetic association studies designed to investigate acquired arrhythmias. Received: May 22, 2001 / Accepted: June 8, 2001     

Observation of CSF pulsatile flow in MRI--the signal void phenomenon

In a comparative study of MR images of 289 neurosurgical patients, loss of the signal intensity (signal void phenomenon) of CSF in the aqueduct was observed in 77 patients. This signal void phenomenon was seen most frequently in infants with chronic subdural hematoma (12 of 18) and patients of all age groups suffering from communicating hydrocephalus (10 of 14). It is known that CSF in the cranial cavity flows toward the spinal CSF space in to and fro manner responding to brain parenchyma pulsations. The velocity of this flow is to be faster in the narrower parts through the ventricular systems such as the aqueduct, Monro's foramen and the 4th ventricles. We think that in T2 weighted images signal void phenomenon reflects "high velocity signal loss" due to CSF flow. When the subarachnoid adhesions secondary to subarachnoid hemorrhage stagnate CSF flow in the subarachnoid space, the intraventricular CSF flow forms the main buffer for changes of the brain volume. This causes an increase in the amplitude of the pulsatile flow in the ventricular systems. Therefore the signal void phenomenon in the aqueductal CSF becomes more pronounced. It may be possible to differentiate normal circulation of CSF from abnormal with the bigger amplitude of CSF pulsatile flow, to understand the mechanisms of the normal pressure hydrocephalus or to diagnose a shunt malfunction. Therefore more insight in the CSF flow as imaged by MRI is needed, quantification of CSF flow will be the subjects of our further research.     

"Ductectatic" mucinous cystadenoma and cystadenocarcinoma of the pancreas

Five cases of localized cystic dilatation of a side branch of the main pancreatic duct due to a new entity ("ductectatic" mucinous cystadenoma and cystadenocarcinoma) are reported. The dilated duct was widely covered by epithelium indistinguishable from that of mucinous cystadenoma (n = 4) or cystadenocarcinoma (n = 1) of the pancreas. All lesions were located in the uncinate process and were about 3 cm in size. On computed tomographic scans and sonograms, lesions were difficult to distinguish from simple cyst of the pancreas unless lobulated or irregular margins were demonstrated. Endoscopic retrograde pancreatography (ERP) or operative pancreatography clearly demonstrated characteristic findings: localized, prominent cystic dilatation of a side branch of the main pancreatic duct with grape-like clusters or pear-shaped pools of contrast material associated with filling defects of various sizes. When a cystic lesion is noted in the uncinate process of the pancreas, ERP is mandatory to confirm or rule out this potentially or overtly malignant disease.