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Biomedical subjects

A Saul

Publications and source records attributed to A Saul.

At least 163 records · Page 9Linked to original sources
PubMed1984

Decreased membrane deformability in Melanesian ovalocytes from Papua New Guinea.

We examined the ability of Melanesian ovalocytes from Papua New Guinea to be deformed in order to probe the resistance of these cells to invasion by several species of malaria parasite. We found ovalocytes were refractile to drug-induced endocytosis, that they formed abnormal rouleaux, showed reduced deformability when aspirated into 0.6-micron diameter pores in polycarbonate sieves, and failed to crenate when mounted under a glass coverslip. No substantial differences were found between normocytes and ovalocytes in their initial rate of filtration through 4.5-micron pore polycarbonate sieves, their membrane fluidity as measured by the rate of depolarization of fluorescent probes or the rate of extraction of cytoskeletal proteins in low ionic strength buffers. We conclude that the resistance of ovalocytes to undergo localized deformation might be significant in explaining the resistance of these cells to invasion by malarial merozoites.

Chlorpromazine↗
PubMed1984

An affinity technique for the isolation of Clostridium perfringens type C from man and pigs in Papua New Guinea.

Necrotising enteritis caused by Clostridium perfringens type C (CwC) is an important cause of morbidity and death in highland regions of Papua New Guinea (PNG) and the organism is readily isolated from clinical cases. Although detected in fluorescent antibody stains of faecal cultures, CwC has previously only once been isolated from normal people or from pigs in PNG. The difficulty results from the greater numbers of the much more common Cl. perfringens type A (CwA) which is morphologically and culturally indistinguishable from CwC. Separation of CwC from the more numerous CwA has been achieved by utilising their antigenic dissimilarity. Silicate beads covered with specific antibody to CwC added to a mixed culture bound CwC cells while most of the unbound cells were washed away. When the beads were plated out type C organisms were recovered. In laboratory tests CwC was isolated from mixtures with CwA where the type A organisms predominated by one million to one. With this system type C organisms have been isolated from human and pig faeces from PNG.

Animals↗
PubMed1984

A high molecular weight antigen in Plasmodium falciparum recognized by inhibitory monoclonal antibodies.

Inhibitory monoclonal antibodies which bind to some isolates of Plasmodium falciparum from Papua New Guinea, but not from other areas, bound to a 220 kD antigen. By immunofluorescence microscopy this antigen was shown to be located both within the schizont cytoplasm and also within the schizont infected erythrocyte, but external to the schizont itself. Even at antibody concentrations which caused greater than 70% inhibition of parasite multiplication, accumulation of schizont stages or aggregates of merozoites were not seen, consistent with inhibition occurring at a point after the release of merozoites. While this suggests that the antigen may be present on merozoites, the quantity was below the limit of detection. It is suggested that the large amount of antigen released by rupturing schizonts may be a mechanism used by the parasite to evade immunological attack.

Animals↗
PubMed1983

The synthesis and fate of stage-specific proteins in Plasmodium falciparum cultures.

Cultured ring, trophozoite and schizont stages of Plasmodium falciparum were metabolically labeled with [35S]methionine. After labeling, cultures were incubated for varying times in the presence of non-radioactive methionine. Triton-soluble proteins from different stages of growth were analysed by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Most proteins were synthesized by every stage of growth and remained unchanged throughout the cycle through to the ring stage following merozoite invasion of erythrocytes. At least 15 proteins, most of high molecular weight, were synthesized solely or predominantly by schizonts. Eight proteins (approx. 177, 170, 158, 87, 83, 47, 41 and 24 kDa) appeared in schizonts but not merozoites. Eight proteins (approx. 240, 203, 106, 80, 35, 19, 15 and 14 kDa) appeared in merozoites, but not in rings following merozoite invasion. Some proteins appeared to be modified after synthesis.

Amino Acids↗
PubMed1983

Effects of ultraviolet irradiation on the cell cycle in normal and UV-sensitive cell lines with reference to the nature of the defect in xeroderma pigmentosum variant.

Analysis of the distribution of cells through the phases of the cell cycle by DNA flow cytofluorimetry has been utilized to investigate the effects of ultraviolet (UV) irradiation on cell-cycle progression in normal and UV-sensitive lymphoblastoid cell lines. In time-course studies only slight perturbation of DNA distribution was seen in normal cells, or UV-sensitive familial melanoma (FM) lines in the 48 h following irradiation. Xeroderma pigmentosum (XPA) excision-deficient cells showed a large increase in the proportion of cells in S phase 16-40 h post-irradiation. XP variant (XPV) cells were blocked in G1 and S phases with the complete absence of cells with G2 DNA content 16-28 h after irradiation. By 48 h post-irradiation the DNA distribution of XPA and XPV cells had returned to that of an unirradiated control. When colcemid was added to the cultures immediately after irradiation to prevent mitotic cells dividing and re-entering the cell cycle, progression through the first cycle after irradiation was followed. UV irradiation did not affect the rate of movement of cells out of G1 into S phase in normal, FM or XPA cells. The proportion of cells in S phase was increased in UV-irradiated cultures in these cell types and the number of cells entering the G2 + M compartment was reduced. In UV-irradiated cultures of XPV cells a large proportion of cells was blocked in G1. The rate of accumulation of cells with G2 DNA content was equal to that of the control until 4 h post-irradiation, thereafter falling below the control. Thus XPV cells in S phase at the time of irradiation complete DNA synthesis to reach G2 DNA content. However, cells irradiated in G1 are blocked from entry into S. These results suggest that there is a defect in XPV cells that affects a step prior to the onset of DNA replication.

Cell Cycle↗
PubMed1983

Resistance of Melanesian elliptocytes (ovalocytes) to invasion by Plasmodium knowlesi and Plasmodium falciparum malaria parasites in vitro.

Erythrocytes from humans with Melanesian elliptocytosis are resistant to invasion by Plasmodium falciparum in vitro and epidemiological evidence suggests they may be resistant to P. vivax and P. malariae. We have examined the ability of P. knowlesi merozoites to invade Melanesian elliptocytes in vitro as a definitive means of examining these cells for resistance to invasion by malarial species with different receptor requirements. The Melanesian elliptocytes were highly resistant to invasion by P. knowlesi merozoites showing that the resistance associated with this erythrocyte variant lies at a level common to the invasion pathway(s) of P. falciparum and P. knowlesi. This makes Melanesian elliptocytosis unique as no other human erythrocyte variant has been shown to be resistant to invasion by both species.

Elliptocytosis, Hereditary↗
PubMed1982

An automated assay of merozoite invasion of erythrocytes using highly synchronized Plasmodium falciparum cultures.

Plasmodium falciparum cultures were synchronized using three lytic treatments with sorbitol. Schizonts from these cultures were used in a rapid, highly sensitive assay of invasion of erythrocytes by merozoites. The parasitaemias in recipient cells after invasion were determined by flow cytofluorimetry after staining with the dye 33258 Hoechst. Invasion of erythrocytes was shown to be reduced by serum from a patient with malaria. The assay is suitable for rapidly screening large numbers of samples, such as monoclonal antibodies.

Animals↗
PubMed1982

Antigenic differences among isolates of Plasmodium falciparum demonstrated by monoclonal antibodies.

Hybridomas raised against two Papua New Guinea (PNG) isolates of Plasmodium falciparum secreted monoclonal antibodies which bound to schizonts of all seven PNG isolates tested but not to schizonts of four non-PNG isolates from Thailand, Nigeria, Ghana, and The Netherlands. Some of the monoclonal antibodies were tested for their ability to inhibit the growth of one PNG isolate, one Thai isolate, and one Nigerian isolate in vitro. Only the growth of the PNG isolate was inhibited, thus demonstrating functional antigenic differences among isolates of P. falciparum.

Animals↗
PubMed1982

Purification of mature schizonts of Plasmodium falciparum on colloidal silica gradients.

The density of human erythrocytes infected in vitro with Plasmodium falciparum has been measured by isopycnic centrifugation in colloidal silica gradients. The densities of uninfected cells, rings, trophozoites, young schizonts, and mature schizonts were approximately 1.110, 1.110, 1.106, 1.097, and 1.090 g/ml, respectively. This information has been used to design a simple procedure for the separation of schizonts from other parasite stages and uninfected erythrocytes. By using synchronized cultures it is possible to obtain essentially pure schizonts after two centrifugations using a bench centrifuge. Such preparations are an excellent source of parasite antigen for immunological studies.

Centrifugation↗
PubMed1981

Ovalocytic erythrocytes from Melanesians are resistant to invasion by malaria parasites in culture.

Ovalocytic erythrocytes from Melanesians in Papua New Guinea have been demonstrated to be resistant to infection by malaria parasites (Plasmodium falciparum) in culture by using a double-label fluorescence assay of merozoite invasion. That merozoites do not bind irreversibly to ovalocytes has been demonstrated by an assay that measures competition between ovalocytes and normocytes. Analysis of behavior on thermal deformation has demonstrated that ovalocytes are more more thermostable than normocytes, suggesting that there is a major difference in cytoskeletal structure. These findings with P. falciparum and epidemiological data demonstrating clinical resistance to P. vivax and P. malariae suggest that the membrane alterations(s) in these ovalocytes affect(s) invasion step(s) common to all three species of malaria parasite.

Animals↗
PubMed1981

Ovalocytosis in Papua New Guinea -- dominantly inherited resistance to malaria.

Analysis of ovalocytosis in families has demonstrated dominant inheritance. This conclusion is based on finding ovalocytic children of ovalocytic Melanesian mothers and normocytic Caucasian fathers. Inheritance of resistance to thermal deformation and to crenation upon storage correlated with inheritance of ovalocytic erythrocyte morphology. The latter was associated with in vitro resistance to invasion by P. falciparum.

Elliptocytosis, Hereditary↗
PubMed1979

A new permanent tracheostomy tube--speech valve system.

A permanent tracheostoma is often necessary in patients with respiratory diseases such as severe bronchial asthma or chronic bronchitis in order to reduce dead space. Another group of patients who require a permanent tracheostoma are those with laryngeal stenosis or bilateral vocal cord pareses whose general condition makes them unsuitable candidates for more advanced surgical procedures. This has usually been achieved by a conventional tracheostomy tube which, however, carries many problems; the ability to cough is greatly reduced when a sufficient intra-abdominal pressure cannot be acquired, speech is impaired, the tube has to be changed regularly, it must be fixed by bands around the neck, etc. These problems can be significantly reduced by using a short, straight tube placed in the stoma and kept securely in position by an outer flange and four flaps on the tracheal side. To this tube is attached a special two-way valve adjustable for either inspiration and expiration or for inspiration only in which case it also serves as a speech valve. Up to now this construction has been used in 16 patients with excellent results, one patient has had this device continuously since 1970 without any complications.

Aged↗