Evidence that the Receptor for Soluble CD14:LPS Complexes may not be the Putative Signal-Transducing Molecule Associated with Membrane-Bound CD14

Membrane-bound CD14 acts as a receptor for lipopolysaccharide (LPS) on monocytes/macrophages and neutrophils. Studies have suggested that the activation of monocytes/macrophages by the binding of LPS to membrane-bound CD14 may require the association of a signal-transducing molecule with membrane-bound CD14. The observation that non-CD14 expressing cells, such as endothelial cells, can nevertheless be activated by a complex of LPS and a soluble form of CD14 (sCD14) suggests that the receptor for this complex may be identical to the signal transducing molecule associated with membrane-bound CD14. The studies described show that two CD14-specific MoAb are able to block the LPS-induced activation of endothelial cells but do not affect the response of monocytes to LPS. This suggests that the interaction of the sCD14:LPS complex with endothelial cells is distinct from the interaction of membrane-bound CD14 with its putative signal-transducing molecule.     

Acute disseminated encephalomyelitis: the importance of early magnetic resonance imaging

The diagnosis of acute disseminated encephalomyelitis (ADEM) is frequently missed or delayed with consequent delay in instituting therapy in the crucial phase of the illness. The role of MRI in the diagnosis of ADEM is well established, however, the value of its early utilization of treatment on the outcome of patients has not been adequately stressed. Three patients with ADEM are described. Delay in the diagnosis of the first was associated with severe sequelae, while in the other two early diagnosis and institution of corticosteroid therapy which was facilitated by MRI, was associated with a better outcome. MRI should be carried out early once the diagosis of ADEM is entertained.     

Neuropeptides in idiopathic chronic constipation (slow transit constipation)

Tissue specimens from the large bowel of 18 patients with long-standing slow transit constipation were investigated to determine the distribution and density of several neuropeptides and amines in the enteric nerve system, and also of endocrine cells in comparison to normal individuals. CGRP (calcitonin gene-related peptide), galanin, glucagon, GRP (gastrin-releasing peptide), metenkephalin, motilin, neuropeptide Y (NPY), PACAP, peptide YY (PYY), serotonin, somatostatin, substance P and VIP were studied by immunohistochemistry. Tissue concentrations of VIP, substance P and galanin were also measured by radioimmunoassay. Significantly increased VIP, SP and galanin contents were found in specimens from the ascending colon. Levels of VIP and galanin were also increased in the transverse colon. Immunohistochemistry revealed only marginal changes with an increased density of PACAP nerve fibres in the smooth muscle and of VIP and PACAP nerves in the myenteric plexus of the transverse colon. In the descending colon substance P and NPY immunoreactivity were also increased in the myenteric plexus while the density of VIP nerve fibres was reduced in the mucosa/submucosa. The frequency of PYY-containing cells and the 5-HT-containing cells in the ascending colon was significantly increased in the constipated patients.     

High-resolution loading tests in the study of genetic heterogeneity in gangliosidosis fibroblasts

Summary GM₁- and GM₂-gangliosides were isolated from brain and radio-labelled. The labelled moieties were localized by hydrolysis with lysosomal enzymes, followed by thin-layer chromatography of the products. High-resolution loading tests with labelled gangliosides were developed and found to differentiate infantile and juvenile forms of GM₁- and GM₂-gangliosidoses as well as the identification of B, O and AB types of GM₂-gangliosidosis.     

Formation of thrombin-antithrombin III complex using polyamide and hemophan dialyzers.

The recently developed ELISA for the thrombin-antithrombin III complex (TAT) is a sensitive, specific, and simplified means of detecting intravascular coagulation. For further evaluation of the thrombogenicity of a polyamide (P) and a Hemophan (H) hollow-fibre dialyzer a cross-over study was done in ten stable patients on maintenance hemodialysis. At the same doses of heparin (mean bolus of 30 U/kg bw and maintenance doses of 86 U/kg bw), thrombin time and partial thromboplastin time were significantly lower using H. At the end of dialysis TAT was significantly higher in H (mean +/- SEM before HD 3.57 +/- .56, at 240 min 14.9 +/- 6.5 ng/ml, p less than 0.05, Wilcoxon-test) than in P (before HD 4.36 +/- .98, at 240 min 8.95 +/- 3.0 ng/ml, p less than 0.05 H 240 vs. P 240, Wilcoxon-test). Visible clotting was more pronounced in the H filter. Among other favourable features of blood compatibility the polyamide/polyvinylpyrrolidone copolymer with a hydrophilic/hydrophobic microdomain structure has less thrombogenicity. The modified cellulosic membrane H has advantages in complement activation and leukocyte depression, but thrombogenicity seems less favourable since the incorporated diethyl-amino-ethyl groups with their positive charge bind and inactivate negatively charged heparin.     

Immunomodulatory Activity of A Novel Nucleoside, 7-thia-8-oxoguanosine: I. Activation of Natural Killer Cells in Mice

We reported recently that a novel immunomodulator, 7-thia-8-oxoguanosine (7T80G)² inhibited formation of pulmonary melanoma metastases (1), prevented against viral infection in mice (2) and potentiated the efficacy of a weakly immunogenic leukemia vaccine (3). Since certain tumor metastases and virus infected cells are targets to natural killer cells (NK cells), we now investigated whether 7T80G is capable of activating NK cells in mice using NK cell sensitive YAC-1 and B16 and NK cell insensitive P815 targets. CBA/CaJ spleen cells incubated in vitro with 7T80G at concentrations ranging from 0.005 to 0.5 mM responded with increased NK cell activity (32-62 %) compared to controls (4-8%) to YAC-1 targets. Similar levels of augmentation in NK cell activity were observed when 40-168 mg/kg of 7T80G was administered in vivo. In addition to the spleen, 7T80G activated NK cells in the bone marrow (BM), the lungs, the liver, and in peritoneal exudate cells (PE). Although 7T80G elicited activation of NK cells was observed as early as three hours after treatment, the maximal activity was observed after 24 h in the spleen; 12 h in the BM; 48 h in the lungs, and 72 h in PE. Administration of the drug by s.c, i.v., and i.p. routes all induced activition of NK cells in spleen, BM and PE. 7T80G was found to activate NK cells in seven inbred and an outbred mouse strain, suggesting that the induced cytotoxicity against allogeneic and syngeneic tumor cells is not strain specific as well as independent of MHC restriction. C3H/He, CBA/CaJ and BDF/1 displayed higher levels of increased NK cell activity, whereas AKR mice were low responders. Low concentrations of IL-2 (0.25-5 U/ml) that induce little or no NK cell activity, when used in combination with 7T80G, elicited significant enhancement of NK cell cytotoxicity. In contrast, IFN and 7T80G showed no such synergism.     

Gram negative aerobic bacillus pneumonia in oral and maxillofacial surgery--a case for comment.

A case illustrating the potentially fatal complication of endogenous Gram Negative Aerobic Bacillus (GNAB) septicaemia secondary to nosocomial pneumonia is presented along with current theories as to its aetiology. The technique of selective decontamination of the digestive tract is designed and advocated to prevent such occurrences; oral and maxillofacial surgeons should be aware of this approach. It may be, however, that by using much simpler manoeuvres such as changes in policy regarding gastric stress ulcer prophylaxis, the already small risk of such an occurrence will be further reduced. Awareness of this condition will allow a higher index of suspicion when presented with catastrophic septic complications on the ITU and aid in more rational planning of antimicrobial therapy.     

Factors associated with levels of physical activity at work and during leisure time]

Factors associated with levels of physical activity at work and during leisure time were analyzed among 577 subjects who had been selected as population controls for a case-control study by random selection from telephone directories. The intensity of physical activity at work was inversely associated with body mass index, the proportion of professionals & managers, consumption of western style breakfast, coffee, butter/margarine, and whisky; and positively associated with rice intake. Frequency of physical activities during leisure time was positively associated with consumption of vegetables, fruits, mushrooms, milk, cheese and coffee, and moderation in eating; and inversely associated with rice intake and the prevalence of gastrointestinal symptoms and medication. The association of physical activity with these factors should be considered in studying its relationship to disease risk.     

Two-color analysis of lymphocyte subpopulations in patients with nephrotic syndrome due to membranous nephropathy.

Two-color flow cytometry was carried out to determine the correlation between cell-mediated immunity and the levels of proteinuria in 30 patients with membranous nephropathy. Lymphocyte subpopulations were measured by two-color flow cytometry using various monoclonal antibodies of the Leu series. Clinically, the patients were divided into four stages as follows: 1. untreated nephrotic stage, 2. prednisolone (PSL) treated nephrotic stage, 3. persistent proteinuric stage (incomplete remission, ICR) and 4. complete remission (CR). Two-color flow cytometry showed a significant decrease in Leu 2a+15+ (suppressor T) cells and relative increase in Leu 3a+8+ (suppressor inducer T) cells in the untreated nephrotic stage. The mean Leu 3a+8-/Leu 2a+15+ (helper/suppressor) cell ratio was normalized in the persistent proteinuric stage or complete remission after treatment with PSL. Patients with membranous nephropathy showed a significant elevation of Leu 2a+DR+ cells after treatment with PSL. The abnormalities of suppressor T cells and suppressor inducer T cells in the peripheral blood appear to reflect the levels of proteinuria in patients with membranous nephropathy. It was concluded that PSL might stimulate Leu 2a positive cells and then increase the number of Leu 2a+15+ cells in the peripheral blood of patients with membranous nephropathy.