Ysolina M. Centifanto

Herpesvirus Type 2 in the Male Genitourinary Tract

A population study of 190 randomly selected male patients with no history of genital herpesvirus infection revealed a high incidence of herpesvirus type 2 in genitourinary specimens. This indicates that men serve as a reservoir of genital herpesvirus.

THE RELATIONSHIP BETWEEN VIRUS CHEMOTHERAPY, SECRETORY ANTIBODY FORMATION AND RECURRENT HERPETIC DISEASE

One of the unusual characteristics of primary herpes simplex infections is their ability to persist in an-asymptomatic form with only periodic recurrence of disease. infection, neutralizing antibodies are readily produced and the virus usually does not spread; since this virus can pass to adjacent cells, the recurrent form of the disease is usually localized. The conce t of chronicity for these infections was described by Kaufman. p s 2 In his studies on recurrent herpes keratitis, he shaved that the virus is chronically released from periocular tissue and oral structures in the absence of corneal ulcer or mucosal lesions in patient? with high titers of neutralizing antibodies in their serum. This continued active multiplication of herpes simplex virus in the presence of circulating antibodies led us to investigate these phenomena in relation to other defense mechanisms of the body, such as secretory antibodies and interferon. After primary

Effect of 9-(2-hydroxyethoxymethyl)guanine on herpesvirus-induced keratitis and iritis in rabbits.

Drugs used for the inhibition of DNA viruses, such as iododeoxyuridine, adenine arabinoside, or trifluorothymidine, are not biochemically selective in their action and also interfere with normal cellular functions. The recently reported 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) is selectively phosphorylated by viral thymidine kinase but not by normal cellular thymidine kinase. Our present studies show that the acycloguanosine is as effective in treating herpetic keratitis in the rabbit as iododeoxyuridine and trifluorothymidine when given topically as an ointment. It is also effective when given intravenously for the treatment of herpetic iritis and is effective in preventing death from encephalitis in rabbits.

Tilorone Hydrochloride: Human Toxicity and Interferon Stimulation

Summary Tilorone hydrochloride was studied in humans to determine whether it would be a safe and effective interferon inducer in man. Both systemic and topical application failed to produce detectible interferon, and toxicity was noted using both routes of administration. This study indicates that even in the high topical doses, tilorone HCl is neither safe nor effective. Poly I:C has been shown to have a very brief, reduced effect in man as apposed to lower animals. The fact that tilorone, a totally unrelated compound, is very effective in the mouse but not in man suggests that the intrferon system in man may not be capable of intense or prolonged exogenous stimulation and that findings in lower animals may not be applicable to man.

Herpesvirus Type 2: Study of Semen in Male Subjects with Recurrent Infections

Semen from 30 healthy male subjects with recurrent infections with herpesvirus type 2 was obtained when subjects were free of lesions and surveyed by tissue culture for an infectious virus in an attempt to elucidate the transmission of this disease. Inclusion bodies compatible with herpesvirus were found in tissue cultures of semen from 2 participants but an infectious virus could not be cultured directly from any sample. The data suggest that herpevirus type 2 is not ubiquitous in semen of male subjects with recurrent genital infections. The possible role of seminal inhibitors and a defective virus in causing the observed results is discussed, as are the current theories of herpesvirus type 2 transmission.

A Comparison of Serum Immunoglobulins from Patients with Non-neoplastic Prostates and Prostatic Carcinoma

The major immunoglobulin classes were surveyed among 23 patients with carcinoma of the prostate, 14 patients with clinically manifest benign prostatic hyperplasia and 23 healthy, elderly men without evidence of prostatic disease to determine if differences in immunoglobulin levels existed. Levels of IgG,IgA and IgM were determined by single radial immunodiffusion. Serum IgM levels were depressed in patients with all stages of carcinoma of the prostate as compared to levels in controls. These depressions were significant statistically for the tumor group considered as a whole and for patients with stages A and B tumors; the depression of IgM levels in patients with stages C and D tumors bordered on statistical significance. Serum IgG levels were depressed significantly in patients with stages A and B carcinoma of the prostate as compared to controls. Levels in patients with stages C and D lesions exceeded control levels but the difference was not statistically significant. Serum IgA levels in patients with stages A and B tumors were comparable to control levels but levels in patients with stages C and D lesions were significantly higher than controls.

Failure of systemically administered adenine arabinoside to affect humoral and cell-mediated immunity.

The effect of a high dosage (250 mg/kg of body weight) of adenine arabinoside or ara-A (9-beta-D-arabinofuranosyladenine) on humoral immunity was studied in New Zealand white rabbits infected with the McKrae strain of herpes simplex virus. The rabbits were treated daily for 14 days with subcutaneous injections of ara-A. The primary and secondary humoral responses, as measured by neutralizing antibody titers, developed similarly in control and treated groups. Similar drug treatment was used on guinea pigs before or after sensitization with BCG vaccine. Subsequent challenge of the sensitized animals with Old tuberculin solution indicated that ara-A treatment had no effect on the induction or previously established cell-mediated immunity. The lack of immunosuppressive activity of ara-A at dosage levels higher than those used in primates makes this drug a potentially effective agent in the systemic treatment of herpetic infections.

A Therapeutic Antiviral from an Extract of A Infected E. coli (Phagicin).

Summary A new antiviral agent with activity both in vivo and in vitro has been obtained from lambda infected E. coli. A study of the antiviral activity of the lysate in chick embryo monolayers shows that this material is effective in completely suppressing both vaccinia and herpes simplex when added before and as long as 6 hours after infection, and the activity is retained by chick embryo monolayers that have been preincubated with the lysate and were washed thoroughly prior to infection. The lysate does not block absorption of the virus, but rather inhibits intracellular replication. The activity of the lysate is not due to the infective lambda particle per se but to a soluble protein fraction. In vivo, this material has significant therapeutic activity in the treatment of rabbit corneal ulcers.