Modulation of Fas-mediated apoptosis of human thyroid epithelial cells by IgG from patients with Graves' disease (GD) and idiopathic myxoedema

The expression of two autoimmune thyroid diseases, GD and idiopathic myxoedema, is associated with antibodies to the thyroid-stimulating hormone (TSH) receptor. Thyroid stimulating antibodies (TSAb) in GD are TSH agonists and cause hyperthyroidism as well as goitre, whereas thyroid stimulation blocking antibodies (TSBAb) in idiopathic myxoedema are TSH antagonists and cause hypothyroidism and thyroid atrophy. We investigated the effect of antibodies to TSH receptor on Fas-mediated apoptosis of thyroid epithelial cells (thyrocytes). Human IgG was isolated from healthy donors, patients with GD and idiopathic myxoedema. Human thyrocytes were obtained from surgical specimens. Thyrocytes were cultured in the presence or absence of human IgG with or without interferon-gamma (IFN-γ) or IL-1β for a specified time. After incubation, we examined the level of cAMP in cultured supernatants and both Fas and Bcl-2 expression on thyrocytes. In addition, we examined anti-Fas-mediated apoptosis of thyrocytes. Fas expression on thyrocytes was significantly down-regulated by Graves' IgG and TSH, although idiopathic myxoedema IgG did not affect Fas expression on thyrocytes. Idiopathic myxoedema IgG abrogated the effect of TSH on both cAMP production and inhibition of Fas expression on thyrocytes. Treatment of thyrocytes with IL-1β or IFN-γ caused a marked augmentation of Fas expression on thyrocytes. The increase of Fas expression of thyrocytes induced by IL-1β or IFN-γ was significantly suppressed in the presence of TSH or Graves' IgG. Anti-Fas-induced apoptosis of thyrocytes was observed in thyrocytes treated with IL-1β or IFN-γ, but was markedly inhibited in the presence of TSH or Graves' IgG. Furthermore, idiopathic myxoedema IgG abrogated most of the inhibitory effect of TSH on Fas-mediated apoptosis of thyrocytes treated with IL-1β or IFN-γ. Bcl-2 expression of thyrocytes did not change after stimulation with TSH, Graves' IgG, idiopathic myxoedema IgG, IL-1β or IFN-γ. These results suggest that TSAb found in Graves' patients may be potentially involved in the development of goitre by inhibition of Fas-mediated apoptosis of thyrocytes. In addition, TSBAb inhibit the action of TSH and increase the sensitivity toward Fas-mediated apoptosis of thyrocytes, inducing thyroid atrophy seen in patients with idiopathic myxoedema.     

Contact pressure distribution features in Down syndrome infants in supine and prone positions, analyzed by photoelastic methods

BACKGROUND: Local force distribution supporting the bodyweight of infants with Down syndrome (DS) appears to be different from that of healthy controls. The purpose of the present study was to establish methods to assess this force distribution and to allow therapeutic evaluation of neurological development in DS infants prior to walking. METHODS: Contact pressure distribution patterns in supine and prone positions were measured by photoelastic methods and were compared between DS infants and healthy controls. The DS group included eight subjects, seven with regular trisomy 21, and one with a Robertson translocation. The controls consisted of 14 neonates, four 4-month-old infants and eight 7-month-old infants. RESULTS: In both groups, head loading ratio decreased as age advanced but the decrement was less in the test group than in the control group. When the bodyweight loading ratios were measured in two different lying positions, that is, prone and supine, the ratios for prone generally tended to be smaller than those for supine in the controls. This kind of difference between prone and supine was not seen in the DS group. The bodyweight is somewhat sustained with limbs and the limbs loading ratios in the DS group were always significantly lower than in the controls. CONCLUSION: Coordinated development of weight-supporting limbs seems to be poor in the DS group.     

Phagocytosis of heat‐killed Staphylococcus aureus by eosinophils: comparison with neutrophils

Eosinophils are characterized by several functional properties, such as chemotaxis, adhesion, superoxide anion production, and degranulation. In this article, we have studied the role of bacterial ingestion by eosinophils in comparison with that by neutrophils. Eosinophils and neutrophils were purified by using the Percoll gradient method followed by selection with CD16‐coated immunomagnetic beads and centrifugation through a Ficoll‐Hypaque gradient combined with dextran sedimentation, respectively. Both cells were preincubated with anti‐FcγRIIa mAb (CD32 mAb), anti‐FcγRIIIb mAb (CD16 mAb), anti‐CR3 (CD11b mAb), or anti‐CR1 (CD35 mAb) before being examined for phagocytosis of opsonized heat‐killed Staphylococcus aureus (S. aureus). Phagocytosis and production of hydrogen peroxide were simultaneously measured by flow cytometry using S. aureus labeled with propidium iodide and stained with 2′,7′‐dichlorofluorescein diacetate. Eosinophils showed significantly lower activity than neutrophils in both phagocytosis and hydrogen peroxide production. Phagocytosis by both cells was decreased by heat‐inactivated serum. Phagocytosis by neutrophils was significantly inhibited by CD16 mAb and CD32 mAb, whereas that by eosinophils was only inhibited by CD35 mAb. Whereas the mechanism of phagocytosis by neutrophils was mediated by CD16 and CD32, that of eosinophils was modulated by complement receptor 1 (CD35).     

The first report of a patient with interrupted inferior vena cava,multiple post-renal veins and azygos-hemiazygos continuation

The first case of a patient with interrupted inferior vena cava, four post-renal veins and an azygoshemiazygos continuation is presented. The complicated anomalies were omphalocele and atrial septal defect. Cine-magnetic resonance imaging and cardiac catheterization showed an anomalous retroaortic left innominate vein, azygos-hemiazygos continuation in the prerenal portion, arch formed renal vein in the renal portion and four embryonic vessels in the post-renal portion. Combination of these anomalies in the major venous system suggested that the inferior vena cava had failed to form and that the bilateral embryonic venous system, postcardinal and supracardinal veins persisted to be the systemic venous channels.     

Role of vagotony in sinus node dysfunction in children with symptomatic congenital long QT syndrome

The present study examined chronotropic dysfunction and the role of vagotony in congenital long QT syndrome, sinus node function and the effects of parasympathetic blockade. Six patients with congenital long QT syndrome were studied. The four males and two females, aged 1–15 years, had episodes of syncope and malignant ventricular arrhythmias. Congenital long QT syndrome was defined as a corrected QT interval greater than 0.45 s, T wave alternans and the age at diagnosis. The sinus heart rate measured from a 24 h electrocardiograph was abnormally low (< 50 min) in three patients (1, 4 and 5 years old) and did not increase sufficiently with the administration of atropine in five of the six patients with congenital long QT syndrome. From intracardiac electrophysiological studies, the corrected sinus node recovery time was prolonged in three patients and the total sinoatrial conduction time was prolonged in two patients. In most patients who had an abnormally long sinoatrial conduction time and corrected sinus node recovery time, these values returned to normal following atropine administration. In one patient, the corrected sinus node recovery time was prolonged paradoxically by atropine. Sinus node dysfunction in congenital long QT syndrome was affected by vagotony associated with a right sympathetic nerve system abnormality.     

Contribution of pulmonary hemodynamics on manifestation of allergic asthma in patients with congenital heart disease

The purpose of this study was to determine whether pulmonary hemodynamic abnormalities relate to manifestations of allergic asthma. In 448 patients with congenital heart disease the relationships between asthma and age or pulmonary arterial blood (PA) flow were studied. Asthma (allergic and non-allergic) was more common in 39 (19%) of 201 patients with high PA flow, compared with the incidence in those with normal PA flow (6/117, 5%; P < 0.001) and reduced PA flow (1/130, 1%; P < 0.05). In the high PA flow group, the frequency of asthma declined significantly (P < 0.01) with age, from 25–26% in the 6 month-5 year patient group to 5% in the 6–12 year old patients. The frequency of asthma, including allergic type, was significantly (P < 0.01) greater in patients with pulmonary hypertension (15/24, 63%) than in those without (10/77, 13%) at the age of 6 months to 1 year. Asthma in the high PA flow group was associated with other allergic diseases in 30 (77%) of 39 patients, including food allergy in nine (23%), atopic dermatitis in 14 (36%), allergic rhinitis in seven (18%) and abnormally high total IgE levels in 14 (36%). These findings suggest that high pulmonary flow or pulmonary hypertension enhances the manifestation of allergic disease, particularly asthma.     

A case of West syndrome with atypical massive gray matter heterotopia that is well controlled by ACTH therapy

A 4 month old female infant with atypical asymmetrical massive gray matter heterotopia diagnosed as West syndrome is described. Her seizure initially appeared as afebrile general tonic and clonic convulsion and progressed to typical West syndrome consisting of clusters of myoclonic spasms of the extremities, mainly on the left side, accompanied by head and eye deviation to the right side. Electroencephalogram (EEG) presented typical hypsarrhythmia and cranial computerized tomography (CT) and magnetic resonance imaging (MRI) showed massive heterotopic gray matter in the right hemisphere with the same density or intensity as cortical gray matter. Single photon emission computed tomography (SPECT), using N-isopropyl-p-¹²³I-iodoamphetamine (¹²³I-IMP), demonstrated decreased blood flow in the ectopic lesion. Although clinical response to several anti-epileptic drugs was poor, her seizures were well controlled by relatively low dose adrenocorticotropic hormone (ACTH) therapy of 0.015 mg/kg per day followed by a combination of valproic acid and clonazepam.     

Evaluation of a prostate biopsy strategy for cancer detection using a computer simulation system with virtual needle biopsy for three-dimensional prostate models

AIM: We evaluated a prostate biopsy strategy for cancer detection using a computer simulation system with virtual needle biopsy for three-dimensional (3D) prostate models. METHODS: Two 3D prostate models with a volume of 25 cc or 50 cc were constructed from computed tomographic images of radical prostatectomy specimens. The peripheral zone (PZ) and transition zone (TZ) were arranged in the prostate models according to the anatomical information. Four thousand patterns of cancer lesions were automatically inserted into each prostate model with a proportion of 75% in PZ and 25% in TZ. Average hit rates (AHR) in prostate models were evaluated both with an increased number of biopsy cores and various angles of virtual needle biopsy. The influence of adding secondary tumors for hit rates was also evaluated. RESULTS: For both sizes, the laterally angled biopsy in 4-8 core biopsy schemes showed higher AHR than the vertical plane biopsy, while the vertical plane biopsy in 10-18 core biopsy schemes showed higher AHR than the laterally angled biopsy. A higher number of biopsy cores increased the AHR of secondary tumors. CONCLUSIONS: Our results suggest that it is important in prostate cancer detection to change the needle placement according to the number of biopsy cores and the size of the prostate.     

Expression of the Plasmodium berghei ookinete protein Pbs21 in a baculovirus-insect cell system produces an efficient transmission blocking immunogen

A surface protein of Plasmodium berghei ookinetes, Pbs21, was expressed in a baculovirus-insect cell system in cell culture and in Heliothis virescens larvae. Groups of BALB/c mice received two intraperitoneal inoculations of either i) Tris-buffer or homogenized H. virescens larvae infected with wild-type baculovirus; ii) enriched, homogenized ookinetes, or Hi) homogenizedH. virescens larvae expressing recombinant Pbs21 (rPbs21). All animals immunized with ookinetes or with rPbs21 had high litres of antibodies (IgG isotype) that bound to native Pbs21. The large majority of antibodies in immune sera of both groups recognized the antigen under non-reducing but not under reducing conditions. The predominant IgG-sub-classes in mice immunized with ookinetes was IgGl and in mice immunized with rPbs21, the subclasses were IgGl and IgG2a. Immunization with rPbs21 reduced the infec-tivity of P. berghei to mosquitoes by 91% compared to a 99% reduction following immunization with ookinetes. This preliminary data indicate that rPbs21 expressed in this eukaryotic system induces a transmission-blocking immunity which is more effective than that achieved using rPbsll expressed in Escherichia coli (Matsuoka et al. 1994).     

Trichosporon beigelii Pneumonia in a Patient with Malignant Histiocytosis

A 30-year-old previously healthy housewife presented with bilateralpulmonary infiltrates. She was treated with various antibioticsbut died with disseminated intravascular coagulation. Culturesof tracheal aspirates obtained prior to her death yielded Trichosporonbeigelii. Postmortem examination revealed T. beigelii pneumoniawith fungal dissemination in other organs. In addition, manyorgans were found to be infiltrated with atypical mononuclearcells which exhibited cytochemical properties of histiocytes.It was considered, therefore, that T. beigelii pneumonia developedon the basis of underlying malignant histiocytosis. T. beigeliiin her lung sections was fluorescently stained with rabbit antiserumto the fungus isolated from the patient. This is the first reportof Trichosporon beigelii pneumonia associated with malignanthistiocytosis.