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Biomedical subjects

R J Howard

Publications and source records attributed to R J Howard.

At least 307 records · Page 17Linked to original sources
PubMed1982

Studies on the role of red blood cell glycoproteins as receptors for invasion by Plasmodium falciparum merozoites.

The mechanism of invasion of human red blood cells by Plasmodium falciparum merozoites has been studied by several indirect methods. Red blood cells of the S+s+U+ and S-s-U- blood group phenotypes were trypsin treated and their susceptibility to invasion measured. Trypsin-treated S+s+U+ cells lack the portion of glycophorin A which bears the MN blood group determinants but possess glycophorin B, whereas trypsin-treated S-s-U- cells lack both the glycophorin A MN determinants and the glycophorin B molecule. Since the treated S-s-U- cells showed an even greater loss in susceptibility to invasion that the treated S+s+U+ cells, we conclude that glycophorin B does have a role In merozoite recognition, although it appears less important than glycophorin A. Attempts to decrease invasion by pretreatment with glycosidases were unsuccessful, except for the previously reported effect of neuraminidase. N-acetyl-D-glucosamine decreases the appearance of ring-stage parasites after in vitro reinvasion of P. falciparum. However, the persistence of intact and lysed schizont-infected cells when N-acetyl-D-glucosamine was present, several hours after disappearance of these cells from control cultures, leads us to conclude that this sugar has a deleterious effect on terminal stages of parasite maturation. It is therefore not possible to conclude that N-acetyl-D-glucosamine inhibits merozoite attachment and reinvasion specifically by competition for the receptor.

Acetylglucosamine↗
PubMed1982

Surface membrane proteins and glycoproteins of red blood cells from normal and anaemic mice.

1. The surface membrane proteins of red blood cells from normal, hyperbled or acetylphenylhydrazine-treated BALB/c mice and NZB mice of different ages were labelled by lactoperoxidase-catalyzed radioiodination. Sialoglyoproteins were labelled by periodate/NaB3H4 or galactose oxidase +/- neuraminidase/Na3H4 treatments. 2. Anaemia produced several changes in radioiodinated proteins. 3. Sialoglycoprotein radiolabelling was unchanged, even with over 90% reticulocytosis. 4. Decreased periodate/NaB3H4-dependent labelling of red blood cells from Plasmodium berghei-infected BALB/c mice (Howard et al., 1980; Howard & Day, 1981) cannot therefore be due to anaemia per se, but must be related more specifically with infection.

Aging↗
PubMed1982

Radioiodination of parasite antigens with 1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenylglycoluril (IODOGEN): studies with zygotes of Plasmodium gallinaceum.

The iodinating reagent 1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenylglycoluril (IODOGEN) was used to label antigens on zygotes of Plasmodium gallinaceum with parallel studies using lactoperoxidase-catalyzed radioiodination for comparison. Proteins labeled by the IODOGEN method are most probably on the surface of the zygote, as the pattern of labeled proteins analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was very similar to the pattern of lactoperoxidase-labeled proteins. Furthermore, the labeled proteins represented only a subset of the total Coomassie Blue-stained proteins. The radioiodinated zygote proteins were immunoreactive after IODOGEN or lactoperoxidase labeling. The IODOGEN method is technically much more simple than the lactoperoxidase method and does not require the addition of extraneous proteins or H2O2. The advantages of IODOGEN labeling, together with the essential equivalence of results obtained by these two methods, make the IODOGEN method attractive for labeling parasite antigens in general.

Animals↗
PubMed1982

Carcinoid heart disease: diagnosis by two-dimensional echocardiography.

We prospectively studied 14 patients with the carcinoid syndrome to determine if two-dimensional echocardiography could detect the nature and extent of valvular abnormalities. Eight of the 14 patients had definite abnormalities of the right-sided cardiac valves. The tricuspid valve had a characteristic appearance, similar to previously described pathologic findings. The leaflets appeared diffusely thickened, shortened and stiff without evidence of commissural fusion. Saline contrast studies demonstrated tricuspid regurgitation, which corresponded to the severity of the tricuspid valve involvement. The pulmonary valve could only be adequately assessed in seven of 14 patients, and morphologic abnormalities similar to those in the tricuspid valve were found. Follow-up studies have shown progression of cardiac disease in six of eight patients. We conclude that two-dimensional echocardiography can detect the characteristic cardiac abnormalities in the carcinoid syndrome and may be a useful tool for following their progression.

Adult↗
PubMed1982

Altered expression of Plasmodium knowlesi variant antigen on the erythrocyte membrane in splenectomized rhesus monkeys.

Variant antigens are present on the surface of Plasmodium knowlesi malaria-infected erythrocytes as detected by the schizont-infected cell agglutination (SICA) assay. We found that parasitized erythrocytes passaged in splenectomized monkeys did not agglutinate with immune sera. On the first passage from intact to splenectomized monkeys, the SICA titers decreased 4- to 16-fold; after the second and subsequent passages in splenectomized monkeys, the infected cells became nonagglutinable to all sera tested, including sera from animals infected with the nonagglutinating parasites. This loss of agglutinability could have resulted from selection of a genetically distinct subpopulation of the original parasites or the ability of the original parasites to alter their phenotypic expression. We have designated the new nonagglutinable phenotype, SICA [-], and the agglutinable phenotype, SICA [+]. The loss of agglutinability indicates that the variant antigen normally expressed on the erythrocyte membrane of infected cells is altered or absent. Because SICA [-] parasites developed in the absence of the spleen, the major organ of host defense against malaria, then this organ may in some manner influence or modulate antigenic expression in P. knowlesi and possibly other malaria parasites.

Animals↗
PubMed1982

Prospects for the control of host defenses.

Systemic host defenses include phagocytic cells (neutrophils and macrophages), humoral immunity, and cell-mediated immunity. It may be beneficial to increase host defenses to prevent and treat infections, cancer, and often acquired or systemic immunodeficiency disorders. On the other hand, inhibition of immune responsiveness is desirable to prevent and treat rejection of organ grafts, allergic reactions, and autoimmune diseases. There are three general ways to modulate host defenses--pharmacologic agents, radiation, and biologic manipulation. The first two have been most widely applied but lack specificity. Thus, they generally inhibit a variety of immune responses that can lead to undesirable side effects such as infections and cancer. Nonspecificity is generally desirable in stimulating neutrophils and macrophages because it may not be known which bacterium is causing the infection or because several may be involved. Biologic manipulations have the advantage of great specificity but are much more difficult to apply to humans. Some of these types of manipulations that seem to hold promise are stimulators of phagocytosis, immunologic tolerance, control of specific subsets of T lymphocytes, monoclonal antibodies, and interferon. Immune modulation has a price-cancer, susceptibility to infection, toxicity of drugs, serum sickness, anaphylactic reactions, Arthus reaction, and disseminated infection with live viral vaccines.

Animals↗
PubMed1982

Mucormycosis and cutaneous histoplasmosis in a renal transplant recipient.

Mucormycosis of the palate developed in a 31-year-old man while he was undergoing immunosuppression with prednisone and azathioprine after renal transplantation. The infection was excised and did not recur. Ten years later, while still receiving immunosuppressive therapy, cutaneous histoplasmosis of the fingers developed, which was treated successfully with intravenous amphotericin B. The occurrence of mucormycosis and histoplasmosis in this man emphasizes the need to suspect uncommon infections when unusual skin lesions occur in an immunosuppressed patient.

Adult↗
PubMed1981

Invasion of erythrocytes by malaria merozoites: evidence for specific receptors involved in attachment and entry.

Invasion of erythrocytes by malaria merozoites involves attachment of the merozoite membrane at the point of collision with the erythrocytes, then reorientation of the merozoite such that its apex is opposed to the erythrocyte membrane, followed by invaginatin of the erythrocyte membrane and interiorization of the parasite. Specific recognition of erythrocyte surface components by the merozoite has been shown by studies on the specificity of merozoites of different malaria species for a limited range of host-species erythrocytes, for erythrocytes of particular maturity, and for erythrocytes possessing particular blood-group determinants. Different malaria species capable of invading erythrocytes of the same host also exhibit differences in specificity for components on enzyme-treated erythrocytes. The attachment phase of merozoite invasion has been isolated from subsequent steps by treatment of merozoites with cytochalasin B -- they then attach to but do not invade susceptible erythrocytes. There is now evidence for other differences between initial attachment steps and subsequent invasion steps form studies on merozoite treatments in vitro which affect invasion but not attachment. It has also been shown that addition of N-acetyl-D-glucosamine to cultures of Plasmodium falciparum inhibits merozoite invasion. Elucidation of the sequence and nature of molecular interactions of merozoite and erythrocyte membrane molecules during invasion will be based on the fundamental ultrastructural observations and on the specificity of attachment and invasion steps already described.

Acetylglucosamine↗
PubMed1981

Acute acalculous cholecystitis.

Sixty-three patients, 49 men and 14 women, developed acute cholecystitis without gallbladder stones. Only eight patients had a history suggestive of gallbladder disease. In 17 patients cholecystitis developed in the postoperative period, and cholecystitis occurred in 7 patients who had extensive trauma. The signs and symptoms did not differ markedly from those found when acute cholecystitis is associated with cholelithiasis. Pain and tenderness in the right upper abdominal quadrant, vomiting, abdominal distention, decreased bowel sounds, jaundice and fever were common. Thirty (47.6 percent) gallbladder specimens had gangrene, and perforation occurred in five instances. Bacteria were cultured from 28 of 43 bile specimens. E. coli was the most common organism. A high incidence of acalculous gallbladders is found when acute cholecystitis occurs in the postoperative period or after trauma and in children. Decreased blood flow to the gallbladder, cystic duct obstruction and concentrated bile are necessary to produce experimental cholecystitis. These factors are probably necessary in humans also. Decreased gallbladder perfusion caused by shock, congestive heart failure and arteriosclerosis probably contributed to the development of acute acalculous cholecystitis in these patients.

Acute Disease↗
PubMed1981

Studies on malaria in Papua New Guinea: comparison of the surface glycoproteins on red blood cells from infected and uninfected individuals.

The levels of erythrocyte membrane sialic acid from 17 patients with Plasmodium falciparum malaria and 1 with Plasmodium vivax malaria, in Papua New Guinea, have been compared with 9 uninfected controls. The amounts of radioactivity incorporated into the major erythrocyte glycoproteins by the periodate/NaB3H4 or galactose oxidase plus neuraminidase/NaB3H4 methods were unchanged by malaria infection. The electrophoretic mobilities of these proteins also were unaffected. Several new glycoprotein bands with molecular weights (mol. wt) of 160,000, 89,000, 46,000, 42,000 and 33,000 Daltons were labelled on the surface of erythrocytes from infected individuals; however, none of these bands appeared in all malarious samples. Sialic acid levels on the erythrocyte membrane were also measured by exhaustive neuraminidase treatment and quantitative assay of released sialic acid. The amount of sialic acid was raised in 1 infected individual, within the normal range for Europeans in 4 others, and below this range with 3 patients. Apparently, extensive removal or modification of sialic acid on the surface of uninfected erythrocytes does not occur in human malaria, in contrast to the results obtained in earlier studies with the lethal murine malarias.

Adolescent↗
PubMed1981

Kidney allograft survival in dogs treated with total lymphoid irradiation.

Total lymphoid irradiation (TLI) is immunosuppressive and, in rodent, can induce a state where transplantation of allogeneic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. We attempted to apply this treatment to a large animal model. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950-3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned (serum creatinine level less than 2.0 mg/dl) for a mean +/- (SE) of 4.7 +/- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15-76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemagglutinin and in mixed lymphocyte culture was suppressed for at least on month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients.

Animals↗
PubMed1981

Ultrastructural analysis of hyphal tip cell growth in fungi: Spitzenkörper, cytoskeleton and endomembranes after freeze-substitution.

The ultrastructure of freeze-substituted tip cells of Fusarium acuminatum was analysed by conventional and high-voltage transmission electron microscopy (HVEM). At least 2 morphologically distinct types of Golgi-like endomembrane cisternae were observed, each existing as single, fenestrated sheets and tubular elements that were often very closely associated with mitochondria. From HVEM observations of thick (0.25 and 0.5 micron) sections, the Spitzenkörper appeared to correspond to an apical mass of vesicles. A network of microfilaments was identified among component vesicles of the Spitzenkörper and adjacent to developing septa. Microtubules were oriented primarily parallel to the direction of hyphal growth and were located in all areas of the cytoplasm, including the tip cell apex. Cytoplasmic vesicles were closely associated with these microtubules. From these observations it is suggested that cytoskeletal elements play important roles in localized cell wall formation. The filasome, a previously unreported type of coated vesicle in fungi, might also be involved in wall synthesis.

Cytoskeleton↗
PubMed1981

Monoclonal antibodies against a specific surface determinant on malarial (Plasmodium knowlesi) merozoites block erythrocyte invasion.

Twelve hybridoma cell lines secreting monoclonal antibodies against Plasmodium knowlesi merozoites have been produced. Antibodies from 3 of the 12 lines agglutinated merozoites. The 2 monoclonal antibodies (13C11 and 16F8) that markedly agglutinated merozoites blocked merozoite invasion of erythrocytes. Of these 2 lines, the one that induced the most agglutination also blocked invasion most effectively. The third monoclonal antibody (53B3) caused minimal agglutination of merozoites and did not block invasion, nor did the other 9 nonagglutinating antibodies. The 2 blocking monoclonal antibodies bound to antigens around the entire surface of merozoites, as demonstrated by immunoelectron microscopy, and precipitated a single biosynthetically labeled protein of apparent m.w. of 250,000. None of the nonagglutinating lines precipitated this protein. Monoclonal antibodies 13C11 and 16F8 reacted with a common antigenic determinant on a Malaysian and a Philippine strain of P. knowlesi in that they blocked invasion and precipitated a 250,000 m.w. protein from both. Sera from immune monkeys also precipitated this 250,000 m.w. protein.

Agglutination↗