Measles vaccination in primary schools--the Colchester project.
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Biomedical subjects
Publications and source records attributed to M Rao.
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Culture of murine splenic B cells with interleukin 4 (IL-4) caused the up-regulation of the lymphocyte Fc receptor for immunoglobulin E (IgE) (Fc epsilon R) over a similar dose range as required for Ia up-regulation. However, the expression level of the Fc receptor for immunoglobulin G (Fc gamma R) did not increase, rather IL-4 caused a slight but consistent decrease in the Fc gamma R level on the B cells. Fc epsilon R+ B hybridoma cells also responded to IL-4 by exhibiting increased Fc epsilon R expression; with the hybridoma cells Fc gamma R levels were unaffected. IL-4 caused an increase in the number of Fc epsilon R per cell and the highest levels of expression were obtained by having both IgE and IL-4 present in the culture. The specificity of the increase was demonstrated by blocking IL-4-mediated actions with monoclonal anti-IL-4 (11B11). Experiments following the incorporation of [35S]methionine into the Fc epsilon R demonstrated that IL-4 increased the rate of Fc epsilon R biosynthesis; this provides an explanation for the IL-4-induced increase in Fc epsilon R expression. IL-4, unlike IgE, had no effect on the rate of degradation of the Fc epsilon R. Interferon-gamma (IFN-gamma) totally abrogated IL-4-mediated Fc epsilon R up-regulation; at the same concentration of IFN-gamma Ia up-regulation is also suppressed, although not as effectively. IFN-gamma was shown to directly suppress Fc epsilon R synthesis, thereby explaining the inhibitory action on Fc epsilon R levels. Finally, it was shown that 11B11 inhibited the increased expression of Fc epsilon R on B cells obtained from mice during the early, but not the late, stages of Nippostrongylus brasiliensis infection. This latter finding suggests that the high Fc epsilon R levels seen early in parasite infections are dependent upon IL-4. The results overall provide further insight into the biologic activities of IL-4.
Rodent B cells respond to culture with IgE by increasing their IgE-specific Fc receptors (Fc epsilon R). The mechanism of this upregulation was characterized on Fc epsilon R+ murine B cell hybridoma lines. Measurements of [35S]methionine incorporated into the Fc epsilon R over time indicated that IgE did not appreciably increase the rate of Fc epsilon R synthesis. In contrast analysis of Fc epsilon R decay from surface radioiodinated B hybridoma cells demonstrated that IgE acted to slow the rate of Fc epsilon R degradation. Very little endocytosis of monomeric IgE was seen; this, combined with the observation that lysomotropic agents failed to inhibit Fc epsilon R degradation suggested that decay occurs at the cell surface. A soluble receptor immunoassay was developed, using monoclonal anti-Fc epsilon R, and this assay demonstrated that cell-bound IgE inhibited the release into the culture media of soluble immunoreactive Fc epsilon R. Examination of the soluble Fc epsilon R by SDS-PAGE after isolation with monoclonal anti-Fc epsilon R demonstrated that it was 10,000 m.w. smaller than the cell-associated Fc epsilon R. IgE affinity columns failed to bind the Fc epsilon R fragment, indicating that the ligand binding activity was largely lost. Thus this study demonstrated that IgE-dependent Fc epsilon R induction on B cells occurs because IgE upon binding to the B cell surface, inhibits the proteolytic cleavage and release of the Fc epsilon R into the surrounding medium, and it is this inhibition of degradation that causes the higher Fc epsilon R levels.
A rat hybridoma producing a high-affinity IgG2a monoclonal antibody (B3B4) directed against against the murine lymphocyte IgE receptor (Fc epsilon R) was established by using purified Fc epsilon R from Fc epsilon R+ murine hybridoma B cells as immunogen. The monoclonal and polyclonal anti-Fc epsilon R inhibited the binding of IgE to the murine lymphocyte Fc epsilon R and were also used to isolate the Fc epsilon R. B3B4 specifically recognized only the 49-Kd Fc epsilon R on murine B lymphocyte as determined by immunoprecipitation and SDS-PAGE analysis. In addition to its reaction with intact Fc epsilon R, B3B4 also recognized Fc epsilon R fragments that were present in the culture media of Fc epsilon R+ hybridoma cells. The predominant fragments isolated were 38 Kd and 28 Kd by SDS-PAGE analysis. When tested for reactivity with other cell types, B3B4 was highly specific for murine B lineage cells in that it did not significantly react with Fc epsilon R on macrophages and T cells and, in addition, did not react with the high affinity mast cell Fc epsilon R. B3B4 completely blocked IgE rosetting, and a reciprocal inhibition of binding was seen in a dose-dependent fashion between IgE and B3B4, indicating a close proximity of the IgE and B3B4 binding sites. Saturation binding analysis indicated that the Fab' fragment of B3B4 bound to twice as many sites/cell as IgE, suggesting that there are two identical B3B4 determinants per 49-Kd Fc epsilon R or that the IgE binding site is formed by the association of at least two 49-Kd Fc epsilon R. However, unlike IgE, neither B3B4 nor F(ab')2-B3B4 nor Fab'-B3B4 were very effective in causing Fc epsilon R upregulation on murine hybridoma B cells; in fact, B3B4 prevented this upregulation when added in combination with IgE. These results suggest that a site-specific interaction provided only by IgE may be essential for ligand-specific upregulation. Both polyclonal and monoclonal antibodies will be useful in further studies concerning the functional relationship between the membrane Fc epsilon R and the soluble Fc epsilon R fragments.
The synthesis of phosphatidylethanolamine was accomplished when a mixture of phosphatidic acid, ethanolamine, and cyanamide at pH 7.3 was taken to dryness and heated at temperatures ranging from 25 to 60 degrees C for 6 h. Chromatographic, enzymatic, and chemical techniques were used to identify and confirm that phosphatidylethanolamine had been formed. This work indicates that the synthesis of this compound can occur starting with precursors and conditions that are presumed to have existed on the primitive Earth.
There have been anecdotal reports describing patients with systemic lupus erythematosus (SLE) and inappropriately elevated secretion of antidiuretic hormone (ADH), but no systematic studies of ADH and its metabolism in SLE have been performed. We measured plasma ADH levels in 36 stable SLE patients with normal renal function and examined the relationship of the circulating ADH concentration to clinical disease activity and effective extracellular fluid volume as reflected by peripheral plasma renin activity (PRA) and plasma aldosterone concentration. The mean ADH level was elevated, 11.4 +/- 1.0 microU/ml (normal 0.4-1.4 microU/ml), while mean PRA and aldosterone were 5.4 +/- 0.6 ng/ml/h and 10.6 +/- 1.6 ng/100 ml, respectively. When patients were divided into two groups according to disease duration, those with SLE for 2 years or more had significantly higher plasma ADH levels (13.9 +/- 1.4 vs. 7.7 +/- 0.9 microU/ml; p less than 0.001 and urinary osmolality (697 +/- 63 vs. 445 +/- 49 mosm/kg; p less than 0.02) compared to those with SLE of less than 2 years duration. No differences in serum Na+, K+, PRA, plasma aldosterone concentration, C3, or 24-hour urinary protein excretion were noted between these two groups. Six patients with SLE for less than 2 years underwent a standard water load (20 ml/kg); in 3/6 there was a paradoxical increase in the plasma ADH concentration. These findings indicate that SLE is associated with elevated plasma ADH levels that increase with prolonged disease duration. This abnormality is unrelated to the usual serologic indices of SLE activity, effective extracellular fluid volume status, or any apparent renal unresponsiveness to ADH.(ABSTRACT TRUNCATED AT 250 WORDS)
The synthesis and ligand-dependent regulation of the lymphocyte receptor for IgE (Fc epsilon R) has been studied. Using murine Fc epsilon R+ cell lines, a 44-kilodalton 35S-methionine-labeled Fc epsilon R precursor was isolated by immunoaffinity chromatography. In contrast to the final processed 49-kilodalton Fc epsilon R, this precursor cannot be isolated from IgE affinity columns, indicating the importance of this processing in the function of the Fc epsilon R. The IgE-mediated Fc epsilon R upregulation was also studied and it was demonstrated that the degradation rate of the Fc epsilon R was dramatically slowed by ligand occupation of the Fc epsilon R. This degradation involves the cell surface-mediated release of a 38-kilodalton Fc epsilon R fragment that can be isolated using monoclonal anti-Fc epsilon R antibodies. Thus, these results demonstrate that posttranslational processing is required for the lymphocyte receptor to gain significant IgE-binding capacity; once acquired its degradation is slowed by occupation of the Fc epsilon R with ligand. At least in the rodent model system, this slowing of the degradation helps explain the increased Fc epsilon R levels seen in the presence of high IgE levels.
This new line of thinking may open up a horizon for management of usually an unrewarding problem. The role of drainage surgery in early cases is stressed as a first line of action, followed if necessary by pan-retinal photocoagulation.
Proteases were detected in aqueous extracts of Dirofilaria immitis microfilariae. Enzymes within the extract were capable of hydrolyzing Azocoll, a general protease substrate, at pH's 7, 8, and 9. Sensitivities to a variety of protease inhibitors indicated that multiple azocollytic enzymes were present in the extract, most prominent of which appear to belong to the serine class of proteases. By incorporating various substrates into the matrices of polyacrylamide gels, 2 SDS-resistant, mercaptoethanol-sensitive proteases in the MF extract were identified at 22 and 76 kDa. These proteases showed differential abilities to digest casein, fibrinogen, hemoglobin, and IgG. The MF extract hydrolyzed radiolabeled IgG into 8-10-kDa fragments following a 20-hr incubation. A similar degree of digestion was observed in 2 hr when viable microfilariae were used. The potential significance of these proteases in the evasion of host effector mechanisms is discussed.
We investigated the antidiuretic hormone (ADH) response in 12 infants with bronchopulmonary dysplasia during acute respiratory distress. All of the infants had hypoxemia with air-trapping in the chest at the time of admission to the hospital. None had documented infection. There was a dramatic increase in the plasma levels of ADH during acute respiratory distress, with a subsequent reduction of levels toward normal when the respiratory distress decreased to the preadmission well state. Three of 12 infants manifested hyponatremia at 24 hours after admission, with two of them exhibiting persistent hypertension for up to three days. The mechanism for elevated ADH levels is air-trapping in the chest, causing pulmonary hypovolemia and decreased left atrial filling and/or decreased transmural pressure of the left atrium.
A prospective study of primary drug-resistant strains of Mycobacterium tuberculosis among children was begun at the Kings County Hospital Medical Center of Brooklyn in 1961 and reported at 5 4-yr periods through 1980. The present report extends our observations of primary drug-resistant tuberculosis in children through 1984. The salient finding in the present report was the increase in primary drug resistance to rifampin, 3 of 19 strains resistant in the last period of study (1981 to 1984) as compared with 1 of 96 strains isolated in the previous 3 periods of study (1969 to 1980). This increase was significant (p less than 0.02) even though the number of strains isolated was small. There were continued low resistance rates to ethambutol and para-aminosalicylic acid and stable resistance rates for isoniazid and streptomycin.
Rat basophilic leukaemia (RBL) cells are known to possess three different kinds of receptors capable of interacting with IgE, which have been named R, H and 71K and which differ in apparent molecular weight (MW) as determined by SDS-PAGE. Reduction of receptors isolated from surface-iodinated RBL cells reduced the MW of 71K to a value corresponding to the MW of R without altering significantly the MW of H or R. Only a single reduction product of 71K could be detected when either surface-iodinated or 3H-leucine labelled RBL cells were used. Analysis of one- and two-dimensional tryptic peptide maps derived from surface-iodinated receptors revealed a similarity between R and 71K. The tryptic peptides of H exhibited an entirely different pattern. These results suggest that 71K consists either of two disulphide-linked R-like molecules, or of one such molecule linked to another as yet undetected polypeptide chain.
The purpose of this study is to compare the drug-susceptibility patterns of Mycobacterium tuberculosis isolated from patients (children) and from their corresponding adult contacts. We wished to ascertain if the susceptibility pattern of the isolate from the adult contact could be used as a guide in the initial selection of the antituberculous drug regimen in the child. Strains resistant to one or more antituberculous drugs were emphasized in our study. For 120 children with positive cultures, adults were identified who had positive cultures and who were the source of the children's infections. All strains had susceptibility tests for isoniazid, streptomycin, aminosalicylic acid, ethionamide, and, when they became available, ethambutol and rifampin. There were 29 instances in which either the adult's and/or the child's strain were resistant to one or more antituberculous drugs. In 111 (92.5%) instances the organism isolated from the child and that from the adult contact had identical drug-susceptibility patterns. Fourteen (93%) of 15 of the adult/child pairs were both resistant to isoniazid. The drug-susceptibility pattern of isolates obtained from the source of a child's illness is useful as a guide in planning initial drug therapy. In addition, knowledge of isoniazid-resistant strains in adult contacts may alert the physician to the potential failure of isoniazid prophylaxis.
The pollen of Parthenium hysterophorus, an alien weed growing wild in India was found to be a potential source of allergic rhinitis. A clinical survey showed that 34% of the patients suffering from rhinitis and 12% suffering from bronchial asthma gave positive skin-prick test reactions to Parthenium pollen antigen extracts. Parthenium-specific IgE was detected in the sera of sixteen out of twenty-four patients suffering from seasonal rhinitis. There was 66% correlation between skin test and RAST.
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A 3-year retrospective review of 110 consecutive Tenckhoff catheter placements was undertaken. Major complications were found in 3.6 per cent of cases and minor complications occurred in 30 per cent. Analysis of cases in which catheters failed revealed that obesity and prior abdominal surgery occurred in 75 per cent of these patients. Attention to these factors and the use of appropriate techniques of placement and, in special situations, the use of endoscopy and fluoroscopy have reduced the failure rate of these high-risk situations. Management of infective complications are outlined and should include continued antibiotic dialysis and catheter replacement only if persistent peritonitis or fungal peritonitis occur. With these guidelines, improved peritoneal dialysis can be undertaken with less morbidity to the patient.
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