Neurological aspects of del(1q) syndrome

We have studied three children with de novo terminal deletion of the long arm of chromosome 1 (46,XX,del(1)(q43)). They all have minor anomalies and neurological signs (severe psychomotor developmental delay, generalized hypotonia, and seizures) that have been described previously. In addition, all of these three patients have autistic-like behavior. They avoid eye contact, show no interest in people, express little emotion, and repeat stereotypic movements such as head nodding and purposeless finger manipulation. They also spend excessive time in making unusual sounds consisting of a high-pitched shrill cry with little intonation in infancy and a harsh, strained, and glottal stridency in later life. They make no labial, lingual, or nasal sounds. We suggest that these observations may be unique clinical manifestations of certain terminal 1q deletions.     

ADRENAL PHEOCHROMOCYTOMA WITH BOTH BENIGN AND MALIGNANT COMPONENTS

A case of adrenal pheochromocytoma Is reported characterized by polygonal basophilic granular cells of benign type, plump eosinophilic granular cells of transitional type, and spindle-shaped cells of malignant type. In the primary tumor the neoplastic cells of each type revealed a distinctive topographical distribution. All gradations between the latter two varieties of cells were found, especially in the vicinity of the transitional cell area. Multiple metastases were present in the liver and lungs, where only anaplastic spindle-shaped cells could be found. Ultrastructurally, the benign cells contained predominantly large, rather light, secretory granules with a coarsely granulated core. In the malignant cells, the number, size, and intensity of granules varied considerably from cell to cell or even within a single cell. In general, the malignant cells had a higher frequency of smaller granules with electron-dense homogeneous cores. Moderate amounts of noradrenalin but not significant dopamine or adrenalin could be demonstrated from a metastatic nodule In liver. We postulate that this adrenal medullary pheochromocytoma was benign originally and underwent malignant transformation shortly before the patient's death. This is based upon the patient's clinical features and the peculiar structures of the primary tumor.     

Immunoreactivity of neoplastic and non-neoplastic monocytoid B lymphocytes for DBA.44 and other antibodies.

AIMS--To evaluate the immunoreactivities of neoplastic and non-neoplastic monocytoid B cells (MBC) and compare them with hairy cell leukemia (HCL) and mantle cell lymphoma (MCL). METHODS--An immunohistochemical study of paraffin wax embedded sections was done on surgically resected specimens of spleens with MBC clusters from patients with gastric cancer (14 cases), tonsils (five cases), and lymph node (two cases) showing lymphoid follicular hyperplasia (LFH), submandibular lymph nodes containing MBC in Sjögren's syndrome (one case). Extranodal organs affected by MCL (three cases) and monocytoid B cell lymphoma (MBCL) (seven cases), and spleens from HCL (four cases) were also studied. These specimens were fixed in 10% formalin and routinely processed for paraffin wax embedding. Fresh spleen specimens from patients with liver cirrhosis (one case) and gastric cancer (seven cases) were snap frozen. RESULTS--Mantle zone lymphocytes were DBA.44, CD74 positive and showed a weaker reaction for CDw75 than marginal zone lymphocytes and MBC, which were almost DBA negative. In neoplastic diseases tumour cells in MCL were DBA.44, CD74, and CDw75 positive. MBCL showed a positive reaction for CD74 and CDw75, but positivity for DBA.44 was observed in only one of seven cases. The HCL specimens, all positive for DBA.44, showed a weaker reaction for CD74 and a stronger reaction for CDw75 than either MCL and MBCL specimens. CONCLUSION--These results show that mantle zone lymphocytes and MCL more closely matched HCL for reactivity to DBA.44 than MBC and MBCL. Reactivities for DBA.44 and CDw75 were greater in MBCL compared with its non-neoplastic counterpart, MBC.     

The molecular weight dependence on the photoconductivity of poly(N-vinylcarbazole)

Poly(N-vinylcarbazole), (PNVC), was prepared, fractionated by gel permeation chromatography, and then characterized by viscometry and vapour pressure osmometry. The fractionated PNVC species with relatively narrow molecular weight distributions were successfully used to measure both their electrical dark-conductivity and photoconductivity using a surface type cell in high vacuum (ca. 10^?7 mm Hg) at room temperature. A molecular weight dependent photoconductivity was found for the fractionated PNVCs with weight average molecular weights in the range of 1,2·10³ to 2,4·10⁵. This observation is in contradiction to Epping's results who has found a molecular weight independent photoconductivity in the molecular weight range of 3·10⁵ to 7·10⁶. Our molecular weight dependence may be well understood in terms of the interrupted overlap of the π-electrons of adjacent carbazolyl groups at the terminal parts of the polymer chains, this effect being all the more stronger the smaller the molecular weight is.     

Bacterial lipopolysaccharide acts as an adjuvant to induce autoimmune arthritis in mice

We investigated the ability of lipopolysaccharide (LPS) as an adjuvant to induce autoimmune arthritis. LPS from Escherichia coli was intraperitoneally injected into DBA/1J mice together with the joint cartilage component type II collagen (CII) on day 0. Thereafter, the injection of CII and LPS was continued every 2 weeks up to day 56. The results showed that mice injected with CII plus LPS had signs of arthritis on day 55 and the joint inflammation reached a peak on day 75. Injection of CII or LPS alone induced no arthritis. Histologically, marked oedema of synovium and intense infiltration of inflammatory cells, including neutrophils, were observed 3 days after the onset of joint inflammation. Twenty-one days later, there were marked proliferation of synovial tissues with many mononuclear cells and destruction of cartilage. Anti-CII immunoglobulin G (IgG) and IgG2a antibodies were markedly produced in mice injected with CII plus LPS. Pronounced secretion of cytokines, including interleukins-12 and -1beta, interferon-gamma and tumour necrosis factor-alpha, was also observed in these animals. Arthritis was passively transferred into naive syngeneic mice with sera but not with lymphoid cells from mice given CII with LPS. Other types of LPS from Salmonella enteritidis, Salmonella typhimurium and Klebsiella pneumoniae as well as lipid A from E. coli, induced inflammation in joints when administered with CII. Polymixin B sulphate mixed with LPS or lipid A blocked the induction of joint inflammation. These results indicate that LPS appears to play an important role as an adjuvant in the induction of arthritis in which autoimmunity to CII is involved.     

An analysis of the relationship between aggressiveness and personality traits of children

The purpose of the present study was to understand the concept of aggressiveness of children through an analysis of the relationship between aggressiveness and personality traits. A total of 1,206 elementary school children were enrolled in the study. In order to investigate the correlation, a path analysis was performed using multiple regression analyses in which 4 variables of aggressiveness (irritability, hostility, physical aggression and verbal aggression) were employed as dependent variables and 5 variables of personality traits (agreeableness, conscientiousness, emotionality, openness and extroversion) were used as independent variables. The results of the analysis indicated that significantly positivepath was observed from extroversion to all four variables of aggressiveness. Extroversion indicated especially strong influence on irritability and physical aggression. A significantly negativepath was observed from agreeableness to irritability and hostility. From conscientiousness, a negative path was observed towards physical aggression and a positive path towards verbal aggression. A significantly negative path was observed from emotionality only towards verbal aggression. It was assumed that each of the four inferior characteristics of aggressiveness of children had a complex nature to be influenced by multiple personality traits.     

The roles of soluble osteopontin using osteopontin-transgenic mice in vivo: proliferation of CD4+ T lymphocytes and the enhancement of cell-mediated immune responses.

We generated transgenic mice expressing osteopontin (OPN) under the control of the alpha(1)-antitrypsin promoter. These mice (OPN-T mice) expressed OPN mRNA in liver and kidney, and released a large amount of plasma OPN, which increased after stimulation with turpentine oil. Before sensitization, the number of CD4+ T cells in lymph nodes was significantly higher in OPN-T than nontransgenic mice, and that in spleen was slightly higher, whereas that of CD8+ T cells was no different between OPN-T and nontransgenic mice. After sensitization, the CD4+ T cell numbers in spleen increased significantly, while there were almost no changes in the CD8+ T cells in lymph nodes and spleen. The intensity of contact hypersensitivity responses to 2,4-dinitrofluorobenzene (DNFB) was obviously enhanced in OPN-T mice. In the delayed-type hypersensitivity (DTH) model elicited by DNFB, the number of CD8+ T cells among DNFB-2,4,6-trinitrobenzenesulfonic acid (TNBS)-peritoneal exudate cells was significantly higher in OPN-T than nontransgenic mice, while there was almost no difference in that of CD4+ T cells. Adoptive transfer experiments revealed that the enhanced reactivity is carried by CD4+ and CD8+ T cells, respectively, although the ability of transferring DTH was significantly lower in CD8+ than in CD4+ T cells. The enhancement of CD8+ T cell migration was observed in OPN-T mice. These results suggest that OPN induces a proliferation of effector CD4+ and CD8+ cells in cell-mediated reactions and plays a role in the migration of CD8+ T cells.     

The role of tumor necrosis factor (TNF)-α in the antitumor effect of intrapleural injection of Lactobacillus casei strain Shirota in mice

The involvement of several cytokines in the antitumor effect induced by intrapleural (i.pl.) injection of heat-killed cells of Lactobacillus casei strain Shirota (LC 9018) in mice was investigated. Injection of LC 9018 i.pl. into Meth A fibrosarcoma (Meth A)-bearing mice not only significantly prolonged the survival of the mice, but also effectively inhibited the accumulation of malignant pleural fluid in the thoracic cavity. In the thoracic cavity of tumor-bearing mice treated with LC 9018, we observed large amounts of several cytokines including interleukin (IL)-1β, interferon (IFN)-γ, IL-12 and tumor necrosis factor (TNF)-α. Both anti-IFN-γ and anti-IL-12 monoclonal antibody (mAb) treatments partially diminished the antitumor activity of LC 9018 in vivo, while the treatment of anti-IL-1β mAb did not influence the survival of the mice. However, anti-TNF-α mAb treatment completely abolished the antitumor effect of LC 9018 in vivo, suggesting that in this model LC 9018 has a survival-prolonging effect involving certain cytokines. Moreover, i.pl. injection of mouse recombinant TNF-α into Meth A-bearing mice pretreated with anti-TNF-α mAb partially restored the survival-enhancing effect of LC 9018. These results led us to conclude that TNF-α induced by i.pl. injection of LC 9018 plays an important role in the antitumor effect of LC 9018 in vivo. Received: 22 February 1999     

Effects of growth hormone treatment on thyroid function in pediatric patients with Prader–Willi syndrome

It is unclear whether hypothyroidism is present in patients with Prader–Willi syndrome (PWS). This study aimed to clarify the state of the hypothalamic–pituitary–thyroid axis and the effects of growth hormone (GH) treatment on thyroid function in pediatric patients with PWS. We retrospectively evaluated thyroid function in 51 patients with PWS before GH treatment using a thyroid‐releasing hormone (TRH) stimulation test (29 males and 22 females; median age, 22 months). We also evaluated the effect of GH therapy on thyroid function by comparing serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels at baseline, 1 year, and 2 years after GH therapy. TSH, fT4, and fT3 levels were 2.28 μU/ml (interquartile range [IQR]; 1.19–3.61), 1.18 ng/dl (IQR; 1.02–1.24), and 4.02 pg/dl (IQR; 3.54–4.40) at baseline, respectively. In 49 of 51 patients, the TSH response to TRH administration showed a physiologically normal pattern; in two patients (4.0%), the pattern suggested hypothalamic hypothyroidism (delayed and prolonged TSH peak after TRH administration). TSH, fT4, and fT3 levels did not change significantly during 1 or 2 years after GH treatment. The TSH response to TRH showed a normal pattern in most patients, and thyroid function did not change significantly during the 2 years after initiating GH treatment.     

Contribution of the tdh 1 gene of Kanagawa phenomenon-positive Vibrio parahaemolyticus to production of extracellular thermostable direct hemolysin

Kanagawa phenomenon-positive strains of Vibrio parahaemolyticus contain two copies of the tdh gene (tdh1 and tdh2) encoding thermostable direct hemolysin (TDH). Previous studies suggested that the tdh2 gene, but not the tdh1 gene, was responsible for production of extracellular TDH. In this study, a tdh2-deficient isogenic mutant of Kanagawa phenomenon-positive strain AQ3815 was constructed by a suicide vector-mediated in vivo recombination method. The intact tdh1 gene in the mutant contributed little to Kanagawa phenomenon on Wagatsuma agar but produced TDH in broth media, accounting for 0.5–9.4% of total extracellular TDH of AQ3815.