A monoclonal antibody, MIN/3/60, that recognizes the sulpho-Lewis(x) and sulpho-Lewis(a) sequences detects a sub-population of epithelial glycans in the crypts of human colonic epithelium

Monoclonal antibodies (MAbs) directed to Lewis(x) (Le(x)) and related carbohydrate sequences have been invaluable in anticipating biological roles for these oligosaccharides by detecting the remarkable changes that occur in their expression from the earliest stages of embryogenesis, through development and sequential stages of cell differentiation and maturation. A notable impact has been in the molecular dissection of ligand-receptor interactions in key cell adhesion events at the initial stages of leukocyte recruitment in inflammation, and almost certainly in the metastasis of epithelial tumours. Antibodies that recognise Le(x) and the 3'-sialyl forms were observed to identify leukocyte subsets; these were subsequently found to match those recognized by the leukocyte-endothelium adhesion molecules, the E- and P-selectins. We now describe a MAb (rat hybridoma MIN/3/60) raised to 3'-sulpho-Le(x), a carbohydrate sequence which, in vitro, is bound not only by the E-, L-, and P-selectins, but also by the cysteine-rich domain of the macrophage endocytosis receptor. We observe that MIN/3/60 is bispecific, however; it binds 3'-sulpho-Le(a) as well as 3'-sulpho-Le(x). Nevertheless, our exploratory studies reveal that it may be a useful histochemical reagent when used in conjunction with a monospecific antibody to 3'-sulpho-Le(a). The MIN/3/60 antibody reveals a sub-population of epithelial glycans in the crypts of Lieberkühn in normal human colon.     

克隆化LAK细胞及其培养上清对白血病细胞的细胞毒和分化诱导作用

用半固体－液体两步法克隆的人ＬＡＫ细胞不仅表现对ＮＫ敏感的Ｋ５６２细胞和ＮＫ抵抗的ＨＬ－６０细胞强烈的细胞毒性，在二次杀瘤过程中表现同样高的活性，而且ＬＡＫ细胞培养上清对白血病细胞系ＨＬ－６０和新鲜白血病细胞具有增殖抑制和分化诱导作用。然而不同杀伤活性的ＬＡＫ细胞培养上清对新鲜白血病细胞增殖的影响不同。结果表明ＬＡＫ细胞在直接杀伤白血病细胞的同时，还通过分泌一些活性因子间接影响白血病细胞的增殖和促进其分化成熟，反映了ＬＡＫ细胞抗白血病作用的多向性。     

Sialo-oligosaccharide receptors for Mycoplasma pneumoniae and related oligosaccharides of poly-N-acetyllactosamine series are polarized at the cilia and apical-microvillar domains of the ciliated cells in human bronchial epithelium.

The occurrence and distribution of the sialo-oligosaccharide receptors (sialosyl-I and sialosyl-i) for Mycoplasma pneumoniae as well as other related oligosaccharide structures of poly-N-acetyllactosamine type, and their short-chain analogs based on galactose linked beta 1-4 or beta 1-3 to N-acetylglucosamine (Gal beta 1-4GlcNAc or Gal beta 1-3GlcNAc, respectively) were investigated in the human bronchial epithelium by histochemistry by using sequence-specific monoclonal antibodies and lectins. Among the mature epithelial cells, only ciliated cells were found to express the long-chain antigens, whereas mucus-secreting cells contained the short-chain antigens associated with mucus globules. The long-chain oligosaccharides were found to be highly polarized at the luminal aspects of the ciliated cells where the branched structures (I and sialosyl-I antigens) were detected both at the apical-microvillar border and on the cilia, but the linear structures (i, sialosyl-i, and VIM-2 antigens) were detected exclusively at the apical-microvillar border. These observations provide the first in situ visualization of the receptor structures for M. pneumoniae at the primary site of infection. The lack of sialo-oligosaccharide receptors in secretory cells and the mucus they produce provides a biochemical basis for evasion by this microorganism of the secreted mucus barrier.     

Immunological and histological studies in primary biliary cirrhosis

Thirty-one patients with primary biliary cirrhosis in whom adequate histological liver material was available were studied by immunological and histological methods. There was no statistically significant correlation between individual histological features and the level of serum mitochondrial antibodies. A relationship between the duration of symptoms and histological stage of the disease supports the present concept of its evolution. However, several stages were often identified in the same specimen. Four cases with negative mitochondrial antibodies were similar to the other 27 clinically and histologically.     

Light chain homogeneity of post-infective cold agglutinins

Three post-infective cold agglutinins, two of which were associated with human infection with Mycoplasma pneumoniae were purified and compared with cold agglutinins isolated from three patients with chronic autoimmune haemolytic anaemia (CHA) as regards their immunoelectrophoretic patterns, their light chain types and the appearances of their light chain zones (after reduction and alkylation) in starch gel electrophoresis. One of the M. pneumoniae-induced cold agglutinins was indistinguishable from CHA cold agglutinins for it was monotypic (type-K), had a restricted mobility in immunoelectrophoresis and a narrow, well-demarcated light chain zone in urea formic acid starch gel electrophoresis. The other two post-infective cold agglutinins though bitypic with respect to light chains showed a considerable degree of homogeneity in immunoelectrophoresis and in starch gel electrophoresis they had light chain bands which were sharper than the light chain zone of normal human IgG.     

Peanut lectin and anti-Ii antibodies reveal structural differences among human gastrointestinal glycoproteins

Human gastrointestinal glycoproteins (mucins), isolated by pepsin digestion from foetal stomachs and meconia, and from paired tumour and non-neoplastic mucosal samples of patients with gastric and colorectal carcinomas, were tested for precipitating reactions with peanut lectin (PNL) and four anti-carbohydrate antibodies (two anti-I, Ma and Low, and two anti-i, Den and Galli). There was remarkable correlation between reactivities with PNL and anti-I (Ma): both reagents reacted with non-neoplastic gastric glycoproteins of "non-secretors", but not with those of "secretors", and also with the majority of gastric tumour and meconium extracts regardless of secretor status. Colorectal tissue extracts (with the exception of one tumour extract) reacted with neither reagent. The various precipitating activities, and results of mild acid hydrolysis and affinity chromatography experiments, enable certain inferences to be made regarding the oligosaccharide moieties of gastrointestinal glycoproteins: (a) expression of PNL and anti-I (Ma) determinants in gastric glycoproteins is dependent on secretor status; (b) extracts reacting with PNL and anti-I (Ma) are mixtures of macromolecules: minor populations react with both reagents, or with PNL only; the major population lacks both determinants, or they are masked by other substitutions; (c) determinants reactive with anti-Ii sera other than anti-I (Ma) are less frequently expressed; and (d) colonic glycoproteins in their lack of PNL and Ii determinants. This suggests that there are structural differences in the oligosaccharide backbones of the two types of glycoprotein.     

Granular corneal dystrophy manifesting after radial keratotomy

PURPOSE: To report a case of granular corneal dystrophy after radial keratotomy (RK). METHODS: A 32-year-old man presented with white radial lines in both corneas. He had a history of uncomplicated RK in both eyes 8 years ago. Preoperative refraction had been OD -3.5-0.75 x 180 and OS -3.0-0.5 x 175. The cornea was reported to be clear on postoperative examinations. RESULTS: Postoperative uncorrected visual acuity was OD 20/30 and OS 20/40. Best-corrected visual acuity was 20/25 in both eyes with OD -0.5-0.5 x 60 and OS -0.75-0.5 x 80. Slit-lamp examination revealed discrete well-demarcated whitish lesions with clear intervening stroma in the central anterior cornea consistent with granular dystrophy. Similar opacities were present within the RK incisions. CONCLUSIONS: Production and deposition of such abnormal material could be due to keratocyte activation after RK or proliferation and migration of epithelial cells with a tendency to express abnormal keratoepithelin.     

Familial study of hypertrophic cardiomyopathy and congenital aortic valve disease

A woman with coexisting calcific aortic valve disease and hypertrophic obstructive cardiomyopathy was studied before homograft replacement of the aortic valve and in the second and fourth postoperative years. Postoperative hemodynamic findings, in studies performed with and without pharmacologic agents, were similar to those of patients with hypertrophic cardiomyopathy. Echocardiographic studies 9 years after operation revealed asymmetric septal hypertrophy and systolic anterior motion of the mitral valve leaflet echoes. The patient eventually died from carcinoma of the bronchus 9 years after aortic valve replacement. At autopsy the heart showed the features of hypertrophie obstructive cardiomyopathy. In addition, in the aorta the arrangement of the smooth muscle and elastic fibers was disordered.Subsequently, 10 asymptomatic relatives from four generations of this family were studied clinically and with echocardiography. Unsuspected asymmetric septal hypertrophy was found in four, and the pattern of the aortic valve echoes was compatible with a bicuspid valve in three. Three relatives had coexisting asymmetric septal hypertrophy and a bicuspid aortic valve. This family study shows that hypertrophie cardiomyopathy and bicuspid aortic valve may coexist and may be inherited as a dominant characteristic with variable manifestations.     

Preventive effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite multiple sclerosis: a double blind, randomized, placebo-controlled pilot clinical trial

Multiple sclerosis (MS) presents with optic neuritis (ON) in 20 % of cases and 50 % of ON patients develop MS within 15 years. In this study, we evaluated the preventive effects of vitamin D3 administration on the conversion of ON to MS (primary outcome) and on the MRI lesions (secondary outcome) of ON patients with low serum 25 (OH) D levels. Thirty ON patients (15 in each of 2 groups, aged 20–40 years) with serum 25 (OH) D levels of less than 30 ng/ml were enrolled in a double blind, randomized, parallel-group trial. The treatment group (cases) received 50,000 IU of vitamin D3 weekly for 12 months and the control group (controls) received a placebo weekly for 12 months. Finally, the subsequent relapse rate and changes in MRI plaques were compared between the two groups. Risk reduction was 68.4 % for the primary outcome in the treatment group (relative risk = 0.316, p = 0.007). After 12 months, patients in the treatment group had a significantly lower incidence rate of cortical, juxtacortical, corpus callosal, new T2, new gadolinium-enhancing lesions and black holes. The mean number of total plaques showed a marginally significant decrease in the group receiving vitamin D3 supplementation as compared with the placebo group (p = 0.092). Administration of vitamin D3 supplements to ON patients with low serum vitamin 25 (OH) D levels may delay the onset of a second clinical attack and the subsequent conversion to MS.