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Biomedical subjects

T C Merigan

Publications and source records attributed to T C Merigan.

At least 289 records · Page 16Linked to original sources

Inhibition of multiplication of Mycobacterium leprae by polyinosinic-polycytidylic acid.

Contrary to the results of an earlier study in which polyinosinic-polycytidylic acid [poly(I:C)] administered intraperitoneally to mice had no effect on multiplication of Mycobacterium leprae in the mouse footpad, the local administration of poly(I:C) every 12 h for 15 doses during logarithmic multiplication was found both to inhibit bacterial multiplication and to produce high tissue levels of interferon (IF). Local administration of poly(I) alone inhibited multiplication of M. leprae to almost as great a degree without at the same time producing a measurable IF titer in the footpad tissues. Mouse IF and "mock" IF both inhibited bacterial multiplication to the same degree, but administration of only the former resulted in a measurable IF titer. Polyadenylic-polyuridylic acid administered locally neither inhibited multiplication nor induced IF; fetal calf serum, administered in the same concentration as found in the preparations of IF and mock IF, was modestly inhibitory, without inducing IF. Thus, the local administration of poly(I:C) appears to have inhibited multiplication of M. leprae independently of IF induction.

Animals↗

Interferon inhibition of lymphocyte mitogenesis.

Interferon inhibits the early phase of mitogenic action of Concanavalin A on lymphocytes as measured by incorporation of labelled precursors in RNA, DNA or protein. There was no evidence for a role of cyclic AMP in the process of inhibition. Dialysis of interferon against high salt and urea did not separate cell inhibitory activity from antiviral activity. Thus, these results are compatible with the possibility that the antiviral and cell inhibitory activities are in the same molecule. However, further purification of the interferon will be required to verify this assumption.

Animals↗

Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis.

Four patients with chronic hepatitis B infection and chronic active hepatitis were treated with human leukocyte interferon. Three of them had consistently elevated levels of circulating Dane-particle markers, including Dane-particle-associated DNA polymerase activity, hepatitis B core antigen and Dane-particle-associated DNA. Parenteral interferon administration at a dosage between 6.0 X 10(3) and 17 X 10(4) U per kilogram per day was associated with a rapid and reproducible fall in all Dane-particle markers in the three patients. The suppressive effect was transient when the interferon was given for 10 days or less but appeared to be more permanent when administration was prolonged for a month or more. In addition, long-term interferon therapy was associated with a marked fall in hepatitis B surface antigen in two of three patients and a disappearance of e antigen in two of two patients. Interferon may be useful in limiting carrier infectivity or eradicating chronic infection.

Adult↗

Measles in adults. An unforeseen consequence of immunization?

An outbreak of measles occurred in California in the first half of 1975, especially in the San Francisco Bay area. Of four adult patients with complicated cases, two were receiving immunosuppressive chemotherapy, and both died from a giant-cell pneumonia. The clinical presentation in such cases may be atypical, and special viral isolation and immunofluorescent techniques may be diagnostically helpful. A significant (P less than .0005) trend toward the occurrence of measles in adolescents was observed in this epidemic, which may also occur in future epidemics elsewhere. With wide spread but incomplete immunization, it is possible for the nonimmunized to reach adulthood without acquiring natural infection. As a result, internists as well as pediatricians will have to consider the possibility of measles and be aware of its serious potential in the immunosuppressed patient.

Adolescent↗

Diagnosis of cytomegalovirus pneumonia in compromised hosts.

Sixteen patients with cytomegalovirus pulmonary infection are described. In 11 the diagnosis was made antemortem by lung aspirate or biopsy, and in five the diagnosis was made at postmortem by typical lung histology and positive viral lung cultures. All patients were immunosuppressed by both their underlying diseases and treatment with corticosteroids and other chemotherapy. Although other pathogens were identified at lung biopsy in most patients (73 per cent), primarily Pneumocystis carinii, evidence is offered to demonstrate that cytomegalovirus can cause significant pulmonary disease alone, leading to respiratory failure and death.

Aged↗

Effect of leukocyte interferon on urinary excretion of cytomegalovirus by infants.

Five infants with symptomatic cytomegalovirus infections and high urinary titers of cytomegalovirus were treated with interferon in doses of 1.7-3.5 X 10(5) reference units/kg per day for seven to 14 days. Six courses of treatment were given. One of two infants treated with the largest dose of interferon had transient suppression of viruria; no suppression was noted during the other five courses of treatment. Adverse effects noted included a low rate of weight gain, a transient elevation of serum aspartate aminotransferase and fever. Further trials are needed to determine whether larger doses of a more purified preparation of interferon will eliminate viruria in infants with sytomegalovirus infection, but careful assessment of toxicity will be necessary in this population of patients.

Cytomegalovirus↗

Role of interferon in prophylaxis of rabies after exposure.

Rhesus monkeys were completely protected from rabies by a single dose of experimental, highly concentrated, rabies virus vaccine prepared from virus propagated in cultures of human diploid cells and administered several hours after infection with street rabies virus. Protection seemed to be related to the high antigenicity of the vaccine and to its ability to induce interferon in vaccinated animals. Only partial protection was afforded by one or three inoculations of less concentrated vaccines that were prepared from cultures of human diploid cells or primary hamster kidney cells and that were not capable of inducing interferon. The level of virus-neutralizing antibody induced by vaccination could not be correlated with the final outcome of the disease. The simultaneous inoculation of vaccine and interferon inducers (polyribocytidylic acid homopolymer pair or Newcastle disease virus) did not improve the results obtained with vaccine along, a fact which indicates that factors other than interferon and antibody may play an important role in the treatment of rabies after exposure.

Animals↗

Lymphocyte transformation and interferon production in human mononuclear cell microcultures for assay of cellular immunity to herpes simplex virus.

Interferon production and transformation in response to herpes simplex virus antigen were studied in microcultures of human mononuclear cells. Mononuclear cells consisting of monocytes and both T and B lymphocytes were purified by Ficoll-Hypaque gradients. Lymphocytes, predominantly T with 5% B, were obtained by passage of buffy-coat cells through nylon fiber columns. For some experiments, autochthonous macrophages and column-purified lymphocytes were stimulated with herpesvirus antigen. The effect of specific antibody and cell concentration on reactivity is described. Crude and purified antigens were compared as cell culture stimulants. Significant differences in transformation and interferon were observed between donors with a history of herpes labialis and donors with no detectable antibody, both in cultures prepared by Ficoll-Hypaque gradients and by column purification of lymphocytes. Cultures from seronegative donors prepared by Ficoll-Hypaque gradients produced interferon but did not transform when stimulated by herpes simplex antigen. "Immune" interferon production, that is, type II as opposed to type I, occurred only with autochthonous macrophage and column-purified lymphocyte cultures. Interferon produced by Ficoll-Hypaque-purified mononuclear cultures was type I, and its production was unrelated to immune status. Similarly, column-purified lymphocytes responded to herpes simplex virus antigen with type I interferon if obtained from a seropositive donor.

Antigens, Viral↗

Nosocomial vaccinia infection.

Although hospital-associated spread of vaccinia has been reported in the past, there have been no recent reports. This paper describes hospital-associated spread of vaccinia virus infection, supplies data on the environmental survival of vaccinia virus and offers recommendations for the management of patients with vaccinia that may minimize the hazard of infection in other high-risk patients.

Adult↗

Cellular events in zoster vesicles: relation to clinical course and immune parameters.

The cellular responses in zoster vesicles was studied chronologically in 30 patients, some of whom were compromised hosts with disseminated disease. Cell counts were low initially but rose abuptly later. Polymorphonuclear leukocytes predominated at all times in the vesicular fluid and in the cells adherent to the vesicle base. The abrupt rise in the number of cells generally coincided with an abrupt rise in the titer of vesicular interferon; both increases preceded resolution of local infection and cessation of cutaneous dissemination in disseminated disease, but the sequence of the increases was variable. The peak interferon titer correlated with cessation of dissemination better than did peak cell counts, and the timing of the local events contrasted with appearance of complement-fixing antibody, which commonly occurred after the resolution of disease. Possible interpretations are that a few sensitized lymphocytes may initiate the defensive response, produce interferon, and/or produce chemotactic factors that augment the polymorphonuclear response. The appearance of polymorphonuclear cells may be a nonspecific inflammatory response, or these cells or the deeper mononuclear infiltrate seen in biopsies may contribute to the rise in local interferon.

Antibodies, Viral↗

The lact of antiviral effect of (polyinosinic acid): (polycytidylic acid) when attached to insoluble supports.

A local antiviral effect can be observed when (poly rI)-(poly rC), bound to Visking discs by u.v. irradiation, is incubated with monolayers of human foreskin fibroblast cells. Radioactive labelling of cytosine residues in (poly rI)-(poly rC) with -125I, has provided a much more sensitive method for determining the fate of the insoluble (poly rI)-(poly rC) than has been available hitherto. The antiviral effect is not related to the amount of (poly rI)-(POLY RC) present on the insoluble support but rather to the amount of polynucleotide lost from the support during incubation. Treatment of (poly rI)-(poly rC) which had been bound to cyanogen bromide-activated Sepharose with eigher dilute alkali or pancreatic ribonuclease released virtually all the polynucleotide. A small amount of (poly rI)-(poly rC) is released from the insoluble matrix in the presence of serum-free Minimum Eagle's Medium.

Antiviral Agents↗

Randomized trial of transfer factor treatment of human warts.

Dialysed transfer factor, prepared from the leucocytes of a donor whose warts had undergone recent spontaneous regression, was used in the treatment of a child with the Wiskott--Aldrich syndrome. The child then had a spontaneous regression at multiple warty areas. A similar relationship was seen in four otherwise healthy patients in a pilot study. A randomized double-blind study of thirty patients failed to confirm a causal relationship between the transfer factor therapy (equivalent to 2-1 X 10(8) leucocytes) and wart regressions. The need for randomized trials of transfer factor therapy for diseases with a variable natural history is emphasized.

Adolescent↗