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Biomedical subjects

M Joseph

Publications and source records attributed to M Joseph.

At least 199 records · Page 11Linked to original sources

The isolation and characterization of a third or neutral phospholipase A2 in the venom of Agkistrodon halys blomhoffii. An improved fractionation procedure for all three enzymes.

The isolation of a new, third phospholipase A2 from Agkistrodon halys blomhoffi is described. On the basis of a pI value of 6.9, it is termed a neutral phospholipase A2. It was characterized as to its amino acid content, activity towards phosphatidylcholine, heat stability, and hemolytic behavior on human erythrocytes. A comparison of these characteristics with those of the acidic and basic phospholipases A2 established the uniqueness of the neutral enzyme. Two particularly important observations were concerned with the complete stability of the three phospholipases on heating at 100 degrees C at pH 6.0 in the presence of 10 mM Ca2+, but variable stability in the absence of Ca2+, and the significant lack of hemolytic activity by the acidic (pI 4.9) phospholipase A2 as compared to the neutral (pI 6.9) and basic (pI 8.7) enzyme which produced extensive hemolysis of human erythrocytes. Other facets of the characteristics of these phospholipases are discussed.

Animals↗

Inverted papilloma of the nasal septum.

Inverted papillomas are primarily lesions of the lateral nasal wall, but similar papillomas have been observed on the nasal septum. There is controversy as to whether papillomas on the septum should be considered differently from those of the lateral nasal wall and paranasal sinuses. A review of the records of the Massachusetts Eye and Ear Infirmary, Boston, disclosed 18 cases of inverted papilloma of the nasal septum that were treated before January 1968 and January 1980. The histologic diagnosis of inverted papilloma was confirmed by pathologists who examined histologic slides from these cases; these slides had been randomly mixed with slides of nasal vestibule squamous papillomas and slides of inverted papillomas of the lateral nasal wall. Squamous papillomas of the vestibule were readily distinguished microscopically from inverted papillomas of the septum and lateral wall that were histologically similar. The clinical course of these patients suggests that inverted papillomas of the nasal septum behave like inverted papillomas elsewhere and require wide surgical excision and careful follow-up.

Adult↗

Role of anaphylactic antibodies in immunity to schistosomes.

Antibody-dependent cell-mediated cytotoxicity in reinfection immunity to schistosomes in the rat involves either IgG2a anaphylactic antibody and eosinophils or IgE antibody and macrophages. The first system requires two signals, one by the antibody through the eosinophil Fc receptor, another by mast cells through the release of mediators among which is ECF-A. IgE antibody complexed with schistosome antigen binds to an IgE-specific receptor on the macrophage and triggers the cell to release enzymes and superoxide. Immunity in rat schistosomiasis is antibody-dependent, abolished in anti-mu treated neonate rats or by passive serum transfer after selective depletion of either IgG2a or IgE. The two anaphylactic antibody-dependent cell cytotoxicity systems are in a permanent balance in immune rats, eosinophils being blocked by IgG2a immune complexes when this cell is inefficient. Anaphylactic antibodies thus play a key role in triggering and modulating effector cell function.

Animals↗

Enzyme release and superoxide anion production by human alveolar macrophages stimulated with immunoglobulin E.

Human alveolar macrophages specifically released lysosomal beta-glucuronidase and neutral proteases when successively incubated with IgE, and then, for 30 min, with anti-IgE. Superoxide anion O2- generation was obtained when anti-IgE-opsonized zymosan was added to IgE-incubated cells. Macrophages from smokers excreted twice as much enzymes and superoxide as cells from non-smokers. It was possible to induce the specific release of beta-glucuronidase with normal alveolar macrophages successively incubated with the serum of patients allergic to house dust or to grass pollen and then with the specific allergen. This characteristic opens the field to a direct test for allergic sera by analogy with the allergen-induced degranulation test of sensitized basophils.

Allergens↗

Effect of neonatal injection of anti-mu antibodies on immunity to schistosomes (S. mansoni) in the rat.

The effect of neonatally initiated injections of anti-mu serum on immunity to reinfection with Schistosoma mansoni in the rat was investigated in vitro and in vivo. Anti-mu treatment resulting in a profound depression of immunoglobulin synthesis dramatically decreased immunity to reinfection assessed by worm recovery technique. Complement-dependent antibody, IgG2a antibody-eosinophil-mediated and IgE-macrophage cytotoxicity reactions were in parallel markedly reduced. These results show the prominent role played by antibody-dependent mechanisms in immunity to schistosomes in the rat.

Animals↗

IgE antibody-mediated cytotoxicity of rat macrophages against microfilaria of Dipetalonema citeae in vitro.

The Fischer rat develops an acquired resistance against circulating microfilariae. Macrophages from the peritoneal washings of normal rats preincubated at 37 degrees C with the sera obtained from rats immune to circulating microfilariae adhered to and kill the microfilaria of Dipetalonema viteae in vitro within 16 to 24 hr. No significant adherence and cytotoxicity was mediated by sera collected from animals with microfilaraemia or from normal rats. Adherence of macrophages to microfilaria was associated with damage to the surface of the larva as revealed by ultrastructural studies. Neither adherence nor cytotoxicity was induced by preincubation of microfilariae, instead of macrophages with immune serum. The serum factor which mediated adherence and cytotoxicity was heat-labile, but was not a complement component. Immune absorption experiments showed that the relevant serum factor resided in the IgE class of antibody. The immune adherence to D. viteae by macrophages is stage-specific because adherence to infective larvae was not observed whether rate macrophages were preincubated in sera obtained from rats immune to microfilariae or in sera collected from animals after exposure to infective larvae.

Animals↗

Numerical evaluation of facial pattern in children with isolated pulmonary stenosis.

A facial contouring technique, using light sectioning (Cobb, 1972), was modified (Ainsworth and Joseph, 1977) and used in a numerical study of children with isolated pulmonary stenosis (PS) to test the hypothesis that the facial pattern in this condition differs from the normal. Measurements were compared between a group of 20 normal children and a group of 20 children with PS between ages 6 and 10 1/2 years. A distinctive facial pattern emerged. Many anteroposterior measurements were much greater in the PS group, indicating that the tissues were more prominent in the maxillary region. Altogether, 29 measurements showed significant differences (P less than 0.05) between the two groups. Discriminant analyses were carried out to discover which, if any, might be used to predict the group to which an individual should belong. Depending on the variables chosen, between 34 and 37 individuals from the total of 40 were assigned to the correct group--PS or control.

Child↗

Eosinophil-dependent cytotoxicity in rat schistosomiasis. Involvement of IgG2a antibody and role of mast cells.

Using Schistoma mansoni schistosomula collected in vitro and sensitized with 42-day-infected rat serum, normal rat peritoneal cells enriched in eosinophils were proven to subsequently adhere to and kill the schistosomula within 24 to 48 h. The cell-dependent, heat-stable antibody in infected rat serum reached a peak between 30 and 42 days after infection. Inhibition experiments with aggregated immunoglobulins indicated the role of IgG2a antibody in the adherence of eosinophils to sensitized schistosomula. The immune absorption technique showed that IgG2a antibody was involved in the mechanism of cytotoxicity of effector to target cells, whereas the role of IgE antibody could be excluded. Ultrastructural studies revealed the constant presence of eosinophils and mast cells in contact with schistosomula. The use of purified cell populations showed that the cytotoxic effect of the original cell population was significantly decreased after depletion of mast cells and partially restored after addition of mast cells. These observations, together with those concerning the role of IgE immune complexes in macrophage cytotoxicity, suggest the possible participation of anaphylactic antibodies in immunity to schistosomes in the rat.

Animals↗

Cytotoxicity of human and baboon mononuclear phagocytes against schistosomula in vitro: induction by immune complexes containing IgE and Schistosoma mansoni antigens.

Normal human blood monocytes, pre-incubated at 37 degrees C with sera from patients infected with Schistosoma mansoni, strongly adhered to S. mansoni schistosomula in vitro, whereas no significant adherence was induced by sera from uninfected individuals. Comparable adherence occurred with normal baboon blood monocytes or peritoneal macrophages when these cells were incubated with sera from S. mansoni-infected baboons. Adherence of macrophages to schistosomula was associated with damage to the larvae, as estimated by a 51Cr release technique. Neither adherence nor cytotoxicity was induced by pre-incubation of the schistosomula, instead of the monocytes, with immune serum. The relevant factor in immune serum was heat-labile, but was not a complement component. Absorption and ultracentrifugation experiments showed that immune complexes, containing S. mansoni-specific IgE antibody and soluble parasite antigens, produced monocyte or macrophage adherence and cytotoxicity. Similar observations have been reported previously in the rat model. Since the production of large amounts of IgE is a predominant feature of schistosome infections in man and experimental animals, it is possible that this new mode of mononuclear phagocyte activation could act as an immune effector mechanism against S. mansoni.

Animals↗

Circulating antigens and immune complexes in Schistosoma mansoni-infected rats. Characterization by radioimmunoprecipitation-PEG assay (RIPEGA).

Circulating schistosome antigens (CSA) and circulating immune complexes (CLC) were investigated in rats infected with Schistosoma mansoni. The radioimmunoprecipitation-polyethylene glycol (PEG) assay (RIPEGA), with 125I-labelled anti-S. mansoni anti-serum, detected CSA during two distinct periods of the infection; the first between the 11th and the 14th week of infection and the second between the 11th and 14th week after infection. The CH50 deviation test revealed the presence of CIC in sera from infected rats, approximately at the two periods when CSA were detected. At 6 weeks of infection, the levels of CIC in infected rats were not different from those in control rats. However, a more sensitive method characterized IgG2a in C1q-binding C1C from infected rats. At weeks 5 and 6, IgE immune complexes were also detected in the serum from infected rats. In fact, the use of RIPEGA on the material eluted from infected rat serum after passage through an anti-IgE immunosorbent showed the presence of schistosome antigen at week 4, and at higher levels at week 6. Levels of 50% haemolytic complement in infected rat serum were lowered between the 2nd and the 4th week, the 5th and the 8th week and after the 12th week of infection. The possible role played by CIC in the protective mechanisms to a S. mansoni challenge infection in rats is discussed.

Animals↗

Interaction between IgE complexes and macrophages in the rat: a new mechanism of macrophage activation.

In earlier studies we found that normal rat macrophages, preincubated at 37 degrees C with the serum of syngeneic rats immune to Schistosoma mansoni, strongly adhered to S. mansoni schistosomules whereas no significant adherence was induced with serum from normal rat. Using 51 chromium release assay, it now proved that immune serum-incubated macrophages lysed the schistosomules in 18 h. Absorption experiments and ultracentrifugation of the immune serum showed that immune complexes containing specific IgE antibody against S. mansoni and soluble parasite antigens induced macrophage adherence and cytotoxicity. Using various labeling techniques, the binding of aggregated rat IgE to the macrophage surface at 37 degrees C is evident in conditions where endocytosis is neglible. The binding of immune complexes containing IgE antibody to S. mansoni elicits dramatic ultrastructural changes in the macrophage and an increase of its lysosomal enzymes together with specific lytic activity for the schistosomules. The parallel development of immune serum-induced macrophage adherence or cytotoxicity with the level of circulating IgE antibody to the parasite in correlation with the development of immunity in the rat, suggests that this new mechanism of macrophage activation could play a role in immune effector mechanisms against S. mansoni. Therefore, IgE acts as a humoral mediator of cellular immunity.

Animals↗

The plain chest radiograph in infants with an isolated ventricular septal defect.

The plain chest radiographic features of 43 infants with a ventricular septal defect are described. All were under 1 year of age, and cardiac catheter studies confirmed that they had an isolated ventricular septal defect (VSD), so that the RV pressure, size of the shunt and the pulmonary vascular resistance could be related to the radiographic appearances. The radiographs of a number of normal infants of similar age were available for comparison. Four patterns were seen in those with a VSD. In group 1 the radiograph appeared normal. In group 2 there was dilatation of the pulmonary artery and the proximal lung vessels, while in group 3 only the proximal lung vessels were dilated. In group 4 only some of the hilar and proximal lung vessles were dilated, so that the blood distribution appeared uneven.

Cardiac Catheterization↗