DNA vaccine using invariant chain gene for delivery of CD4+ T cell epitope peptide derived from Japanese cedar pollen allergen inhibits allergen-specific IgE response

To establish a new immunotherapy for type I allergic diseases without allergic side effects, we attempted to develop a DNA vaccine encoding both a CD4+ T cell epitope site in a major Japanese cedar pollen allergen (Cry j 2) and an invariant chain (Ii) for the delivery of the epitope peptide into the MHC class II loading pathway. We constructed a plasmid DNA encoding the Ii mutant either by replacement of the core CLIP (class II-associated invariant chain peptide) with a peptide corresponding to the major Cry j 2 CD4+ T cell epitope in BALB/c mice, designated as p247-258 (pCPCJ2), or by fusion of the Ii with p247-258 at the C terminus (pIiCJ2). As expected, repeated inoculation of BALB/c mice with pCPCJ2 or pIiCJ2 induced no antibody response to Cry j 2. In contrast, intramuscular inoculation of BALB/c mice with pCPCJ2 or pIiCJ2 predominantly induced p247-258-specific Th1 cells, resulting in the inhibition of IgE response to subsequent Cry j 2 injections. Our results demonstrated that the plasmid DNA encoding the CD4+ T cell epitope and Ii can induce epitope-specific CD4+ T cell responses in vivo and the potential to regulate type I allergic reaction without allergic side effects.     

Clinical and histopathological significance of PD-1 expression in cutaneous lesions of adult T-cell leukemia–lymphoma

Background

Adult T-cell leukemia–lymphoma (ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection and is known to exhibit cutaneous involvement in 50% or more patients. Few studies have evaluated the clinicopathological significance of programmed death-1 (PD-1) expression in the cutaneous lesions of ATL.

Molecular defects in Krabbe disease

Krabbe disease (globoid cell leukodystrophy) is an autosomalrecessive neurodegenerative disorder that affects both the centraland peripheral nervous systems due to an enzymatic defect ofthe galactocerebrosidase. In this study, molecular defects InKrabbe disease were Investigated In 11 patients (seven Japaneseand four non-Japanese) using cultured skin fibroblasts. A Japaneselate infantile patient had a missense mutation of Pro at codon302 to Ala and a non-Japanese patient had a missense mutationof Val at codon 550 to Gly. The reduced enzymatic activitiesexpressed from the cDNAs with these missense mutations and fromthe previously reported nonsense mutation (E369X, Glu at codon369 to stop codon) were confirmed. Genomic DNA analyses revealedthat the P302A and E369X mutations were heterozygous and theV550G mutation was homozygous in these patients. A 12 base deletionwith a 3 base insertion was found in three unrelated Japaneseinfantile patients, but not in 30 controls. The mutation washomozygous in two patients and heterozygous in one patient.We could not find any confirmed mutation in the coding regionin the other six patients. These findings suggest that mutationsin infantile and late infantile patients are relatively heterogeneous.     

Phase variation analysis of Coxiella burnetii during serial passage in cell culture by use of monoclonal antibodies

Antigenic changes in Coxiella burnetii Nine Mile strain phase I during serial passages in cell culture were analyzed with three groups of monoclonal antibodies (MAbs) against lipopolysaccharide. The MAbs of group 1 did not react with organisms that were passaged over five times, and the MAbs of group 2 did not react with organisms that were passaged over eight times. The MAbs of group 3 reacted with organisms passaged up to 15 times but did not react with phase II cells. These results suggest that C. burnetii could be differentiated into four phase states during phase variation.     

Can group interventions facilitate forgiveness of an ex-spouse? A randomized clinical trial

This study evaluated the effectiveness of 2 versions of an 8-session forgiveness group intervention for divorced individuals. Participants (randomized, n=192; analyzed, n=149) were randomly assigned to a secular forgiveness condition, a religious forgiveness condition, or a no-intervention comparison condition. Measures of forgiveness and mental health were obtained at pretest, posttest, and 6-week follow-up. Participants in both intervention conditions increased significantly more than comparison participants on self-reported forgiveness of an ex-spouse and understanding of forgiveness. Participants in the secular condition showed a greater decrease in depressive symptoms than comparison participants. Intrinsic religiousness did not moderate intervention effects.     

TCR-alpha chain-like molecule is involved in the mechanism of antigen-non-specific suppression of a ubiquitin-like protein.

Although existence of suppressor T cells is a controversial issue in cellular immunology, several lines of evidence indicate that T-cell-receptor alpha-chain (TCR-alpha) is a critical component of suppressor factors produced by these cells. Monoclonal non-specific suppressor factor (MNSF), a lymphokine produced by murine T-cell hybridoma, possesses pleiotrophic antigen-non-specific suppressive functions. Recently, we have shown that the 70,000-MW MNSF comprises an 8000-MW ubiquitin-like polypeptide and other subunit(s). Here we report that the 8000-MW ubiquitin homologue is associated with an intracellular TCR-alpha (but not TCR-beta)-like molecule and released from the cells. The affinity eluates obtained from the culture supernatants of E17 cells and concanavalin A (Con A)-activated splenocytes with anti-TCR-alpha monoclonal antibody (mAb) showed an antigen-non-specific, major histocompatibility complex (MHC)-non-restricted suppression. Immunoblot analysis demonstrated that anti-TCR-alpha, but not anti-TCR-beta, mAb recognizes native 70,000-MW MNSF. In addition, we found the dissociation of the 8000-MW polypeptide from the 62,000-MW TCR-alpha cross-reactive protein by hydrolase which cleaves isopeptide bonds. Thus the covalent attachment of ubiquitin-like protein(s) may be involved in the underlying mechanism of suppressor T-cells and TCR-alpha-like molecule(s) might be a main link between antigen-specific and non-specific suppression.     

Hormonal and Genetical Assessment of a Japanese Girl with Weaver Syndrome

We report a case of Japanese girl with a rare disorder of Weaver syndrome, which was characterized by overgrowth with advanced and disharmonic bone age, craniofacial abnormalities, developmental delay, metaphyseal flaring of the long bones and camptodactyly. The patient was delivered at 38 weeks of gestation with a length of 54.2 cm (+ 2.6 SD), a weight of 3805 g (+ 2.5 SD) and an occipitofrontal circumference (OFC) of 35.0 cm (+ 1.1 SD). She manifested hypertonia and flexion contractures in the first few years. She also had submucosal soft cleft palate and difficulty in swallowing and breathing in early infancy. When she was 5 years and 7 months old, her height and weight were 133.3 cm (+ 5.5 SD) and 32.0 kg (+ 5.1 SD), respectively. We could not detect any endocrinological abnormalities for the cause of overgrowth. According to clinical features, Weaver syndrome was suspected and genetical analysis was performed. Fluorescence in situ hybridization (FISH) and direct sequencing analysis showed neither deletion nor point mutation of the nuclear receptor SET-domain-containing protein 1 (NSD1) gene on 5q35, which is responsible for Sotos syndrome. Therefore, we made a diagnosis of Weaver syndrome for this patient and discussed the differential diagnosis in terms of overgrowth syndrome.     

Differential flotation centrifugation study of hepatitis C virus and response to interferon therapy

Hepatitis C virus (HCV) appears to circulate in various forms such as native virion, immune complexes, and nucleocapsids during chronic infections. To determine the association of the physicochemical properties of HCV and its response to interferon therapy in patients with chronic hepatitis C, we examined pretreatment serum samples from 43 patients with HCV RNA who had received interferon therapy, using differential flotation centrifugation in a NaCl solution with a density of 1.063 g/ml. After centrifugation, the ratio of HCV RNA in the top and bottom fractions was determined by the polymerase chain reaction and expressed as T/B. Patients with a sustained response to IFN therapy were found to have higher T/B ratios than transient responders who relapsed after treatment (P < 0.01) and nonresponders (P < 0.01). With regards to HCV genotypes, patients with genotype 1b had higher T/B ratios in the sustained response group than in the nonsustained response group (P = 0.001), but patients with genotype 2 had a similar distribution of T/B among the 3 response groups (not significant). These findings indicate that the physicochemical properties of HCV affect the effectiveness of interferon therapy, particularly in patients with genotype 1b. J. Med. Virol. 52:190–194, 1997. © 1997 Wiley-Liss, Inc.     

Lack of Constrictive Effects of Cocaine on the Fetal Ductus Arteriosus in the Rat

Cocaine (12.5 or 25 mg/kg) was administered intraperitoneally to pregnant rats 15 min to 12 hr prior to Caesarean section on day 20 of gestation. The fetuses were immediately frozen and serially sectioned, and the diameter of their ductus arteriosus (DA) was calibrated. The DA was patent in all the fetuses examined and the DA caliber was not significantly different between the control and the cocaine-treated groups at any time interval after the cocaine dosing. It was concluded that cocaine has no constrictive effects on the fetal DA in the rat.     

Impact of progressive fibrosing interstitial lung disease (ILD) in ILD patients complicated with secondary spontaneous pneumothorax

Background:Secondary spontaneous pneumothorax (SSP) in interstitial lung disease (ILD) may influence prognosis of any ILD, and SSP onset predicts poor outcome in idiopathic pulmonary fibrosis (IPF). Recently, progressive fibrosing ILD (PF-ILD) has rapidly acquired importance.Objective:We hypothesized that PF-ILD would strongly influence the prognosis of patients with any ILD complicated with SSP.Methods:We retrospectively surveyed and collected data from patients hospitalized for SSP from January 2016 to June 2020. PF-ILD was defined as the following occurring within 24 months before SSP develops: relative decline in %forced vital capacity (FVC) ≥10% or two of the following: relative decline in %FVC between 5% and 10%, worsening respiratory symptoms, or increased extent of fibrosis on high-resolution computed tomography.Results:We analyzed 32 patients hospitalized for SSP in ILD. This study comprised 18 patients with PF-ILD and 14 patients with non-PF-ILD. PF-ILD patients had lower body mass index (BMI) and %FVC. No significant differences in survival regarding follow-up period from the time of ILD diagnosis and hospitalization for SSP were observed between the PF-ILD and non-PF-ILD patients. Older age and lower BMI were significant predictors of mortality by multivariate Cox regression analysis. ROC analysis showed BMI ≤17.8 kg/m² to reliably predict poor prognosis.Conclusions:Regardless of whether patients have PF-ILD, older age and lower BMI in patients with ILD places them at higher risk of developing SSP, and prognosis is poor if SSP develops. Therefore, clinical management of physique is important to improve the prognosis of ILD patients.