A homozygous MITF mutation leads to familial Waardenburg syndrome type 4

Waardenburg syndrome (WS) is a genetic disorder characterized by hearing loss and pigmentary abnormalities with variable penetrance. Though heterozygous mutations in MITF are a major cause for Waardenburg syndrome type 2 (WS2), homozygous mutations in this gene and the associated phenotype have been rarely characterized. In this study, we identified a novel p.R223H mutation in MITF in a Chinese Han family with variable WS features. Both parents carried a heterozygous p.R223H mutation. They had normal hearing, and premature greying of the hair is their only pigmentary abnormality. In contrast, their two children both carried a homozygous p.R223H mutation and had classic WS features including profound hearing loss, heterochromia irides and marked pigmentary abnormalities in hair and skin. Interestingly, the two affected children also have persistent chronic constipation since the neonatal period, symptoms suggestive of Waardenburg syndrome type 4 (WS4). Our study revealed a likely association between homozygous mutations in MITF and WS4, which implies a dosage effect for the underlying pathogenesis mechanism.     

抗SARS病毒N蛋白单克隆抗体的制备和初步应用

目的 制备抗SARS病毒N蛋白的单克隆抗体并研究其初步应用。方法 用基因重组N蛋白免疫小鼠，取免疫后的鼠脾细胞与骨髓瘤细胞融合，筛选分泌抗SAPS病毒N蛋白单克隆抗体细胞株。将阳性细胞株接种小鼠腹腔制备单克隆抗体腹水并对抗体进行纯化，分析纯化抗体的相对亲和力。选择亲和力较高的抗体制备检测SARS病毒抗原的酶联免疫诊断试剂，并对其敏感性和特异性进行分析。结果 共获得11株单克隆抗体细胞株，其中3株单抗与N蛋白具有较高的亲和力，4株纯化单抗与N蛋白反应很弱，其余4株单抗介于两者之间。用亲和力较高的单抗制备检测SARS病毒抗原的诊断试剂，其敏感性可达31PFU／ml，而且与其他呼吸道病毒无交叉反应。结论 该试剂特异性较好，可用于SARS病毒抗原的检测，其敏感性仍需用临床急性期样品进行评价。     

EXTEROCEPTIVE STIMULATION AS A CONTINGENT FACTOR IN THE INDUCTION AND ELICITATION OF DELAYED TYPE HYPERSENSITIVITY REACTIONS TO 1 CHLORO-, 2-4, DINITROBENZENE IN GUINEA PIGS

This study attempted to determine whether a prior period of “stress” would elicit the sensitization reaction of the skin to topically applied chemical agents. A subthreshold concentration of 1-chloro-, 2-4, dinitrobenzene (DNCB) was applied to the skin of 40 guinea-pigs, 20 of which had been subjected to repetitive electrical shocks throughout the previous 15 minutes. They were examined 24 hours later, and were retested with DNCB at another site after 9 days for signs of delayed sensitization. The stressed animals exhibited a more severe contact-reaction (p <. 01) after the induction test and also after the delayed test.     

The hand-foot-genital syndrome: on the variable expression in affected males

Fryns JP, Vogels A, Decock P, Van den Berghe H. The hand-foot-genital syndrome: on the variable expression in affected males.
Clin Genet 1993: 43: 232–234. © Munksgaard, 1993
In this report we document male-to-male transmission in the hand-foot-genital syndrome. An affected father transmitted the syndrome to his three sons. A grade IV hypospadias, which was the most severe genital anomaly in affected males, was present in the youngest, moderately mentally retarded microcephalic male sibling.     

A Preliminary Study of Immunotherapy with a Monomethoxy Polyethylene Glycol Modified Honey Bee Venom Preparation

Monomethoxy polyethylene glycol (mPEG) modified honey bee venom (HBV) immunotherapy (IT) has been studied in 14 patients allergic to honey bee venom. Doses could be increased more rapidly and higher doses were reached compared to regular venom immunotherapy. No general side effects were seen, although large local swellings were found somewhat more often than with regular HBV. Most patients could easily be switched from the modified to the unmodified venom. Eight patients experienced and tolerated field stings. Skin testing showed a decreased allergenicity of the mPEG-HBV. The mean HBV-specific IgE level was below pre-treatment level already after only 6 weeks of IT. The HBV-specific IgG response was very good.     

HLA-A,B,C and DR antigen frequencies in acquired immunodeficiency syndrome (AIDS) patients with opportunistic infections

During the past three years, an epidemic of acquired immunodeficiency syndromes (AIDS) involving the presence of specific forms of cancer (notably Kaposi's sarcoma) and infection (e.g., pneumocystis carinii) ordinarily seen only in severely immunosuppressed hosts has occurred among active homosexuals, Haitian immigrants, drug users, and hemophiliacs in large cities in the United States and elsewhere. An as yet unidentified viral agent is presumably the cause of the initial immunodeficiency and host genetic factors may influence the subsequent development of different clinical symptoms in different patients. We have previously reported that the HLA antigens DR5 and DR2 are associated with susceptibility to Kaposi's sarcoma (KS) in different Caucasian subpopulations. We now have also noted that AIDS patients with opportunistic infections have a normal frequency of DR2 and DR5 and a significantly increased frequency of DR3 and that the ultimate clinical expression of AIDS in patients with unexplained lymphadenopathy may depend upon genetic factors associated with these particular DR types.     

The mechanism of hyperlipidaemia in the nephrotic syndrome

The mechanism of hyperlipidaemia in the nephrotic syndrome has not been fully established. We propose that it results from hypoalbuminaemia due to inhibition of the reaction catalysed by lecithin cholesterol acyltransferase converting cholesterol of high density lipoproteins to cholesterol esters and to an inhibition of high density lipoprotein particle formation from very low density lipoproteins due to reduced activity of lipoprotein lipase.     

Changes in lymphocyte chromatin in Down's syndrome revealed by the thermal denaturation method

A luminescence-microscopic study using acridine orange with a short-term culture of human cells showed that DNA melting profiles of the chromatin of intact lymphocytes of healthy donors are curves with maxima (F 530) in the temperature regions of 45, 65, 78, 85, 88, and 92°C (P<0.01). The melting profiles of lymphocytes of patients with Down's syndrome are curves with maxima in the temperature regions of 65, 85, 88, and 92°C (P<0.01). The absence of a decrease in the intensity of fluorescence between 78 and 85°C is evidently due to the greater degree of condensation of certain regions of the chromatin complex of the trisomic cells. The possible mechanisms of the structural changes in the interphase chromatin, of human lymphocytes under the influence of temperature are discussed.Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 6, pp. 672–674, June, 1976.     

Head circumference of children with Williams-Beuren syndrome

Head circumference is considered an important parameter of brain growth and development. Syndrome-specific standards for head circumference in Williams-Beuren syndrome (WBS) are not available to date, although mental retardation is a leading manifestation in the syndrome. Therefore, we investigated head growth in 63 girls (251 measurements) and 88 boys (298 measurements) with WBS between birth and adulthood. Most measurements in both sexes were from the first 4 years of life (n = 162 in girls and n = 189 in boys). Mean (±SD) head circumference at birth was 33.39 ± 1.38 cm and 34.02 ± 1.44 cm for term girls and boys, respectively. Although head growth in WBS girls and boys was at a slower velocity, the pattern of head circumference was similar to that in the normal population. After the age of 3 months, head circumference started to fall below the normal mean in girls (0.5–2 cm). In boys, mean head circumference was below the normal mean already at 1 month of age (2 cm). The deficit increased to 3 cm from 6 months to 4 years. Adult OFC was 52.85 ± 1.75 cm (n = 16) compared to 55.70 ± 1.83 cm (n = 46; P < 0.00001) in WBS women and 55.51 ± 1.68 cm (n = 30) compared to 57.87 ± 1.29 cm (n = 31; P < 0.00001) in WBS men. During development, microcephaly is only seen in about one third of WBS patients. © 1994 Wiley-Liss, Inc.