Genetic control of anti-thyrotropin receptor antibody generation in H-2K mice immunized with thyrotropin receptor-transfected fibroblasts.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
H Niimi
Publications and source records attributed to H Niimi.
Jansen-type metaphyseal chondrodysplasia: analysis of PTH/PTH-related protein receptor messenger RNA by the reverse transcriptase-polymerase chain method.
Jansen-type metaphyseal chondrodysplasia (JMC) has both delayed ossification in long bones and usually hypercalcemia. We report a Japanese male patient with JMC who presented with rachitic signs on radiographs, hypercalcemia (13 mg/dl) and low %TRP at age 3 months (mo). Hypercalcemia was treated from age 3 mo to 11 yr. Progressive widening, splaying and fragmentation of the metaphyses have been recognized on radiographs which resulted in shortened tubular bones and consequent short stature [107 cm (-6.5 SD)] at age 13 yr. Hypercalcemia tended to normalize, and %TRP became normal at age 13 yr. Repeated measurements of serum PTH and PTH-related protein (PTHrP) levels showed that they were low or normal in the face of hypercalcemia and high urine cAMP excretion, which led us to suspect constitutive activation of the PTH/PTHrP receptor. Direct sequencing of PTH/PTHrP receptor complementary DNA from skin fibroblast cells revealed a CAC to CGC transversion yielding a strictly conserved His223 to Arg substitution found in 90% of DNA fragment in the second transmembrane domain of the receptor. This mutation created a restriction site Sphl (G/CATG/C). Direct sequencing of genomic DNA and also restriction enzyme digestion revealed heterozygous transition. The mutation was absent in the parents with normal phenotype. We conclude that both dysplastic bone lesions and calcium homeostasis are age-dependent in JMC, and that the His223-Arg substitution is the same as that found in four Caucasian patients with a similar phenotype irrespective of the ethnic difference, and that the preferential expression of an abnormal allele of the PTH/PTHrP receptor mRNA in skin fibroblast despite heterogygotic transversion in the genomic DNA suggests the importance of allele expression.
Dwarfism↗
Association of HLA-DR, DQ genotype with different beta-cell functions at IDDM diagnosis in Japanese children.
Japanese IDDM patients have been demonstrated to have unique and different HLA associations from white patients. To elucidate the effect of HLA-associated genetic factors on the clinical heterogeneity of IDDM in Japanese people, HLA-DRB1, DQA1, and DQB1 genotypes in 88 childhood-onset Japanese IDDM patients were examined by polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) or sequence-specific primers (SSP). Of the 88 IDDM patients, 26 (29.5%) had DRB1*0405-DQA1*0302-DQB1*0401/X (DR4-DQ4/X), 38 (43.2%) had DRB1*0901-DQA1*0302-DQB1*0303/X (DR9-DQ9/X), and 9 (10.2%) were DR4/9-DQ4/9 heterozygous in the present study (X does not contain protective alleles). Clinical heterogeneity such as age distribution at onset, prevalence and serum level of anti-GAD antibodies (GADAb), and residual pancreatic beta-cell function after diagnosis were compared between patients with HLA-DR4-DQ4 and DR9-DQ9. The frequency of DR9-DQ9 genotype was significantly higher in the younger (0-10 years) than in the older (11-16 years) age-group of onset, but the frequency of DR4-DQ4 was higher in the older (11-16 years) age-group. Although no association of DR-DQ genotypes with the prevalence and serum level of GADAb was found among newly diagnosed patients, long-standing DR9-DQ9 patients had significantly higher levels of GADAb than those with DR4-DQ4. While no difference in time course of serum C-peptide (CPR) levels was detected between GADAb+ and GADAb- patients, a remarkable difference was demonstrated between DR9-DQ9 and DR4-DQ4 patients. The residual pancreatic beta-cell function was retained more in patients with DR4-DQ4 than in those with DR9-DQ9 at diagnosis through 12-18 months after diagnosis. These results suggest that the DR9-DQ9 genotype may induce stronger autoimmune destructive response (T-helper 1 function) against target beta-cells than the DR4-DQ4 genotype does. Our findings may warrant further studies on the association of diabetogenic autoimmune response with HLA class II molecules and contribute to a clarification of interracial differences in HLA-encoded susceptibility to IDDM.
Adolescent↗
Proton MR spectroscopy in Pelizaeus-Merzbacher disease.
Proton MR spectroscopic findings in two patients with genetically defined Pelizaeus-Merzbacher disease revealed ratios of N-acetylaspartate/creatine and choline-containing compounds/creatine that were not significantly different from those found in a population of healthy subjects. These findings suggest that proton MR spectroscopy can aid in the diagnosis of Pelizaeus-Merzbacher disease.
Adolescent↗
[A family of dentatorubral-pallidoluysian atrophy: clinical and neuroradiologic studies].
We described a family of dentatorubral-pallidoluysian atrophy (DRPLA). The mother presented with cerebellar ataxia at 35 years of age and thereafter her neurological symptoms became exacerbated. Her daughter had mental retardation during the preschool period and epilepsy at 10 years. Her son presented with epilepsy at 14 years. Their clinical phenotypes demonstrated maternal anticipation in this family. Genetical analysis of their DNA revealed CAG repeat expansion of the DRPLA gene, the number of which was 51 (mother), 65 (her daughter), and 53 (her son). MR imaging showed disappearance of T, shortening of the red nucleus in the mother and her daughter in contrast to the normal appearance in her son. MR imaging was effective in evaluating neuropathological changes in the DRPLA patients.
Adolescent↗
[Eosinophils in stool smear in normal and milk-allergic infants].
Stool smears of newborn infants were investigated sequentially from birth through 6 months of life in order to study relation between appearance of eosinophils in stool and feeding of babies. In babies born to non-atopic parents, eosinophils appeared in stool smear soon after start of feeding, but disappeared in a short time. Eosinophils were found irrespective of types of feeding, i.e., breast feeding, powdered milk or amino acid formula. There was tendency of sustained presence of eosinophils in stool smears in babies born to severe atopic parents. These results suggest that appearance in stool of eosinophils does not necessarily mean allergic reaction to ingested foods and need attention in diagnosing milk allergy. Mechanisms of appearance and function of eosinophils in stool in normal babies may differ from those in pathological situations and need further detailed investigation.
Breast Feeding↗
[Successful treatment of interstitial pneumonia with lipo-PGE1 and pentoxifylline in a patient with dermatomyositis].
Interstitial pneumonia complicated with dermatomyositis sometimes shows a resistance to high dose steroid therapy and a fatal course particularly in patients without showing the elevation of creatine kinase. We experienced a 48 year old woman who developed heliotrope rash, Gottron's sign, multiple cutaneous ulcers, and dyspnea on exertion. These symptoms were resistant to low dose steroid therapy. Serum levels of creatine kinase were normal. Anti-nuclear antibodies and anti-Jo-1 antibody were negative. High resolution CT scan of the chest showed areas of multiple air space consolidation and subpleural linear shadows. Lung biopsy performed under video-assist thoracosurgery revealed diffuse alveolitis with scattered lymphoid folicules and mild accumulation of macrophages in the alveolar spaces. There were no honey-combing. These features were compatible with "non-specific interstitial penumonia" proposed by Katzenstein, 1995. The patient was treated with 10 micrograms lipo-PGE1, PGE1 incorporated in lipid microspheres, and 300 mg pentoxifylline, which resulted in a dramatic improvement of both interstitial pneumonia and cutaneous ulcers. The present case suggested a novel strategy for the treatment of interstitial pneumonia.
Alprostadil↗
[Flow cytometric analysis for the activation of peripheral immunoregulatory cells from patients with bronchial asthma].
By use of flow cytometry, we have investigated intracellular activated eosinophil cationic protein (ECP) in eosinophils and mitogen-induced cytokine production of T cells in peripheral blood from children with acute severe asthma. In addition, we measured ECP releasability (serum ECP/lysate ECP) as a maker of activated eosinophils. The monoclonal antibody EG2 (anti-activated ECP/EPX antibody) was used for measuring the amount of intracellular activated ECP. ECP releasability and mean fluorescence intensity (MFI) values of EG2-positive eosinophils increased at the time of asthmatic attack and reduced after treatment with improvement in peak expiratory flow. Furthermore, the frequency of T cells which produced IL-4, IL-5 and IFN-gamma stimulated with phorbol myristate acetate and ionomycin increased and reduced in parallel with MFI of EG2-positive cells. These observations suggest that flow cytometric analysis for intracellular ECP and mitogen-induced cytokine production reflects the activation of T cells in bronchial mucosa, and is useful for monitoring airway inflammation in bronchial asthma.
Adolescent↗
Involvement of antipain-sensitive protease activity in the interferon-beta-induced UV-refractoriness of Cockayne syndrome fibroblasts.
Fibroblast cells obtained from two siblings and a female patient with Cockayne syndrome (CS), when pretreated with human interferon (HuIFN)-beta prior to irradiation with UV light (254 nm wavelength), exhibited transiently induced fibrinolytic protease activity immediately after the irradiation in association with increased refractoriness to UV cell-killing. A protease inhibitor, antipain, inhibited the induction of protease activity in lysates of the CS fibroblasts from these 3 cases after the combination of HuIFN-beta pretreatment and UV irradiation, whereas elastatinal and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) inhibited the activity less than antipain did. Antipain also suppressed the increase in UV-refractoriness of HuIFN-beta-pretreated CS fibroblasts, as revealed by culturing cells for 24 h in medium containing the inhibitor immediately after UV exposure and thereafter evaluating the ability of colony formation by the cells. Thus, an antipain-sensitive protease may be involved in the UV-refractoriness induced by HuIFN-beta in CS fibroblast strains.
Antipain↗
Induction of Graves-like disease in mice by immunization with fibroblasts transfected with the thyrotropin receptor and a class II molecule.
Graves disease is an autoimmune thyroid disease characterized by the presence of antibodies against the thyrotropin receptor (TSHR), which stimulate the thyroid to cause hyperthyroidism and/or goiter. By immunizing mice with fibroblasts transfected with both the human TSHR and a major histocompatibility complex class II molecule, but not by either alone, we have induced immune hyperthyroidism that has the major humoral and histological features of Graves disease: stimulating TSHR antibodies, thyrotropin binding inhibiting immunoglobulins, which are different from the stimulating TSHR antibodies, increased thyroid hormone levels, thyroid enlargement, thyrocyte hypercellularity, and thyrocyte intrusion into the follicular lumen. The results suggest that the aberrant expression of major histocompatibility complex class II molecules on cells that express a native form of the TSHR can result in the induction of functional anti-TSHR antibodies that stimulate the thyroid. They additionally suggest that the acquisition of antigen-presenting ability on a target cell containing the TSHR can activate T and B cells normally present in an animal and induce a disease with the major features of autoimmune Graves.
Animals↗
T2 shortening in childhood moyamoya disease.
We examined T2 shortening in six children with infarcts due to moyamoya disease to clarify whether there are characteristic patterns of T2 shortening in the deep grey and white matter. Profound T2 shortening in the deep grey and white matter was observed in the acute stage of infarct in two cases, which changed to high intensity in the chronic stage; in this stage no T2 shortening was demonstrated in any case. Neither haemorrhagic infarction nor calcification was seen on CT or MRI. There could be longitudinally different T2 shortening patterns between infarcts due to moyamoya disease and other disorders.
Cerebral Cortex↗
Two novel gene mutations (Glu174-->Lys, Phe383-->Tyr) causing the "hepatic" form of carnitine palmitoyltransferase II deficiency.
Carnitine palmitoyltransferase II (CPT II) deficiency has two different clinical forms, one with "hepatic" and the other with "muscular" symptoms. We studied the molecular basis of the "hepatic" form in two Japanese siblings. Their CPT II activity in lymphoblasts was reduced to 3% of the level observed in normal controls. cDNA analysis showed that the proband was a compound heterozygote. One allele carried a new mutation, G621-->A (Glu174-->Lys). The other carried three single-base substitutions; a new mutation, T1249-->A (Phe383-->Tyr), and two previously reported polymorphisms. The brother had the same four substitutions. Neither of the two new mutations in this study was detected in the 60 alleles of 30 Japanese control subjects. Secondary structure prediction analysis of the mutated CPT II protein was different from that of the normal protein. We concluded that these mutations caused the "hepatic" form of CPT II deficiency in the probands.
Alleles↗
Availability of frequency-selective fat-saturation pulse (Fat-Sat) MRI in childhood optic neuritis.
A 2-year-old boy with acute optic neuritis, confirmed by gadolinium-DTPA enhancement of the optic nerve using frequency-selective fat-saturation pulse magnetic resonance imaging (Fat-Sat MRI), is reported. Because it is difficult in very young children to sufficiently evaluate visual acuity, visual field, and retroocular pain on eye movement, and visual evoked potential during wakefulness, Fat-Sat MRI will be useful for revealing optic nerve inflammation and for monitoring treatment.
Adipose Tissue↗
CT-guided transthoracic needle biopsy: a comparison between automated biopsy gun and fine needle aspiration.
AIMS: We retrospectively investigated the diagnostic accuracy and complication rate of transthoracic core biopsy using an automated biopsy gun and compared the findings with those of aspiration needle biopsy. PATIENTS AND METHODS: Seventy-three patients underwent 74 core biopsy procedures and 50 patients underwent 52 aspiration biopsy procedures. Of these, a final diagnosis was obtained in 107 lesions with surgery or clinical course. Fifteen patients in which a final diagnosis was not obtained were excluded from the study on diagnostic accuracy. Thus, in the study of diagnostic accuracy, 63 core biopsy procedures for 62 lesions are included. Core biopsy was performed with an 18 G cutting needle using an automated biopsy gun. Aspiration biopsy was performed with a 20 G aspiration needle. RESULTS: Core biopsy yielded sufficient material in 57/63 procedures (90.5%). A correct diagnosis was obtained in 36 procedures (85.7%) for malignant leisons and a specific benign diagnosis was obtained in 11 procedures (52.4%). Aspiration biopsy yielded a correct diagnosis in 26 procedures (81.3%) for malignant leisons and in seven (46.7%) for benign lesions. The overall correct diagnosis were 75.8% and 71.7% with core biopsy and aspiration biopsy, respectively. Core biopsy gave a higher predictive rate than that of aspiration biopsy for both benign and malignant lessons (P < 0.02). Pneumothorax occurred in 18/74 (24.3%) patients with core biopsy and in 18/45 (40.0%) patients with aspiration biopsy. Of these, three with core biopsy and two with aspiration biopsy needed tube drainage. The other complication was haemoptysis, which occurred in six patients following core biopsy and in three after aspiration biopsy. All nine cases subsided spontaneously. There were no fatal complications. CONCLUSIONS: Core biopsy with a biopsy gun increase the diagnostic accuracy with a higher histologic predictive rate and no obvious additional risk of complications.
Biopsy, Needle↗
A novel human leukaemic cell line, CTS, has a t(6;11) chromosomal translocation and characteristics of pluripotent stem cells.
A novel human leukaemic cell line, designated CTS, was established from the peripheral blood of a 13-year-old girl suffering from acute myeloblastic leukaemia (AML) in relapse. CTS cells expressed CD7, CD13, CD33, CD34 and HLA-DR antigens, and showed ultrastructural myeloperoxidase activity. In addition, CTS cells showed DNA rearrangements of the immunoglobulin heavy chain gene and the light kappa chain gene, and deletions of the T-cell receptor delta 1 gene. Cytogenetic analysis revealed a human female diploid karyotype with a t(6;11)(q27;q23) chromosomal translocation. Molecular studies demonstrated a DNA rearrangement of the MLL gene, the expression of a truncated 11.0 kb MLL mRNA and the detection of the MLL/AF-6 fusion transcript in CTS cells. To our knowledge, this cell line is the first report of a human leukaemic cell line with a t(6;11) chromosomal translocation. CTS cells showed no significant proliferative response to the cytokines, IL-2, IL-3, IL-6, IL-11, GM-CSF, G-CSF, EPO, SCF, but were induced to differentiate to the T-cell, B-cell, erythroid or megakaryocytic lineage in the presence of particular cytokines. This CTS cell line may provide a useful tool in the study of the oncogenesis of mixed lineage leukaemia with 11q23 abnormalities and for the analysis of growth and differentiation of pluripotent stem cells.
Adolescent↗
Diminished interferon-gamma (IFN-gamma) production by bacterial antigen-specific T cells in atopic patients.
In this study, we established and studied cytokine production of T cell lines (TCL) specific to either a purified protein derivative of Mycobacterium tuberculosis (PPD) or Dermatophagoides farinae (Df) from atopic patients and non-atopic healthy subjects. IFN-gamma was detected in the culture supernatants of all of 36 PPD-specific TCL established from healthy controls, whereas only 24 of 38 PPD-specific TCL from patients produced IFN-gamma. Furthermore, the amounts of IFN-gamma produced by PPD-specific TCL from patients were significantly lower than those from healthy controls. No IL-4 was detected in any PPD-specific TCL from either healthy controls or atopic patients. The amounts of IL-4 production from Df-specific TCL from atopic patients were much higher than from healthy controls, while few TCL produced IFN-gamma. These results suggest that the skewing to the Th2-type T cell response in atopic patients is a response not only to allergens, but also to bacterial antigens, compared with non-atopic subjects. Activation of PPD-specific TCL from patients with calcium ionophore A23187 plus phorbol myristate acetate resulted in much higher IFN-gamma production than in TCL established from healthy controls, indicating that the low production of IFN-gamma by PPD-specific T cells from atopic patients is not due to an intrinsic T cell defect but to some regulatory mechanisms.
Animals↗
Allergenic epitopes of ovalbumin (OVA) in patients with hen's egg allergy: inhibition of basophil histamine release by haptenic ovalbumin peptide.
We studied allergenic determinants that induce hypersensitivity to OVA, the major allergen in egg allergy, using immunoblot and histamine release assays. Immunoblot analysis demonstrated a part of the OVA epitope was in the C-terminal region comprising residues 347-385 (OVA347-385). Histamine was released from basophils of a patient with egg allergy upon stimulation with the OVA fragment corresponding to OVA347-385. Furthermore, detailed epitope mapping using overlapping peptides (residues 347-366, OVA-A; residues 357-376, OVA-B; and residues 367-385, OVA-C) in the OVA 347-385 region was carried out using the histamine release assay. In order for histamine release from basophils to occur, the allergen must possess two or more allergenic determinants located on the protein molecule at distances that would be equivalent to the distances between IgE molecules on the membrane surface. these results suggest that there are at least two epitopes that bind IgE antibodies on each OVA peptide. In addition, one epitope that binds IgE antibodies in two patients appears to reside in the haptenic peptide OVA357-366 (OVA-B1). The histamine release from basophils stimulated by OVA-B was completely inhibited by OVA-B1 in one of these patients. Similarly, OVA-B1 inhibited the histamine release produced by OVA-A in the other by more than 40%. These results suggest that haptenic synthetic peptides could regulate the allergic reaction in the effector phase if common epitope(s) recognized by IgE antibodies in the patients with egg allergy can be found. These are the first studies that provide an antigen-specific approach to inhibiting histamine release from basophils by a haptenic peptide recognized by IgE antibodies in an allergic disorder.
Allergens↗
Intractable wheezing in infants with nasopharyngeal reflux.
Two infants with intractable wheezing and moist cough were referred to Chiba Municipal Kaihin Hospital. Their symptoms were persistent even after the usual treatment for respiratory disease. No definite etiological agents were detected. They usually gagged while feeding and barium swallow tests revealed nasopharyngeal reflux and cricopharyngeal incoordination. One of the patients had remarkably high titers of IgE and IgE RAST of cow's milk before she received treatment with thickened formula. She also had peripheral eosinophilia and nasal eosinophilia. These findings were thought to be caused by nasopharyngeal reflux. Four months after therapy commenced, those titers and symptoms were greatly reduced. The clinical and roentgenographic findings in these infants, and their response to therapy, strongly support a causal relationship between nasopharyngeal reflux and wheezing. Therefore, nasopharyngeal reflux should be considered when a baby has intractable wheezing, even when there is no developmental problem.
Deglutition↗