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Biomedical subjects

R J Klein

Publications and source records attributed to R J Klein.

At least 37 records · Page 2Linked to original sources
PubMed1986

Long-term follow-up of serum-interferon and its acid-stability in a group of homosexual men.

For a period of over two years 99 volunteer healthy homosexual men were examined periodically for the presence of interferon (IFN) in their serum. Thirty-nine subjects had either undetectable IFN levels in serum or IFN was detected only once in three to five samples tested. In another 45 subjects low IFN levels were detected throughout the study period. None of these subjects had or developed any disease symptoms. In the remaining 15 subjects high serum IFN levels were detected at their enrollment or during the study period. All these subjects started to manifest clinical symptoms compatible with AIDS. In six subjects the mean time elapsed between the first detection of serum IFN and disease symptoms was 6.5 months. In all subjects but one, the IFN was of type alpha. The acid-stability of serum IFN alpha decreased with time, and when its decrease was abrupt it was associated with a more rapid evolution of AIDS. Sera containing acid-labile IFN alpha can induce IFN alpha synthesis in normal lymphocyte cultures (LC), but do not influence IFN gamma synthesis in LC stimulated with phytohemagglutinin. LC stimulated with viral antigens in the presence of serum with acid-labile IFN alpha synthesized IFN with an increased sensitivity for acid treatment. The results confirm the prognostic value of serum IFN alpha in the development of AIDS, and suggest that the transition to acid-lability may be a gradual process.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine on the acute local phase of herpes simplex virus-induced skin infections in mice and the establishment of latency.

The effect of topical and systemic treatment with 9-(1,3-dihydroxy-2-propoxymethyl)guanine on the evolution of herpes simplex virus-induced skin infection in hairless mice was investigated. Systemic (subcutaneous) treatment with a 10-mg/kg dose and topical applications with a 5% cream started up to 48 h after infection prevented the development of severe skin lesions and a fatal outcome. However, the establishment of latent infections was prevented only by topical treatment started at 6 h after infection. Systemic (50 mg/kg) and topical treatments started 48 h after infection reduced virus titers in the skin and ganglia and promoted rapid clearance of virus from these sites. The clearance of infectious virus from ganglia during the acute phase of infection was followed by early establishment of latency. 9-(1,3-Dihydroxy-2-propoxymethyl)guanine (0.03 microgram/ml) significantly inhibited the synthesis of infectious virus in explant cultures of latently infected ganglia, and at concentrations higher than 8 micrograms/ml no infectious virus was detectable in ganglia explant cultures.

Acyclovir↗
PubMed1985

Established latent herpes simplex virus infections of mice not affected by adenosine monophosphate treatment.

Hairless mice with established latent herpes simplex virus infections in their trigeminal ganglia were treated for different time intervals with various doses of adenosine monophosphate. The treatment did not eliminate the latent infection and the results suggest that the drug did not reduce the amount of reactivatable virus present in latently infected ganglia. It appears therefore that adenosine monophosphate exerts its antiviral effects through non-specific mechanisms.

Adenosine Monophosphate↗
PubMed1984

Protection against establishment of latent infections in mice immunized with a non-pathogenic herpes simplex virus mutant and reinfected with the pathogenic parental strain.

Immunization of hairless mice with a TK-, ACVr, non-pathogenic herpes simplex virus (HSV) type 1 mutant protected the mice against reinfection with lethal doses of the parental pathogenic HSV strain. The protection conferred by the mutant against the establishment of latency after reinfection with the parental strain was dependent on the site of reinfection; after reinfection at the same site, only 2% of mice became latently infected, compared to 32% after reinfection at a distant site. When inoculation with the mutant was done at two different sites, single reinfections at any site led to the establishment of latency in 4% of the mice. The mutant by itself was almost completely latency-negative: only 4.5% of the mice developed latency in trigeminal ganglia and 2.3% in the spinal ganglia. The rate of mutant-induced latent infections is partly related to the dose of the virus; however, lower doses of the mutant may not colonize the ganglia, and therefore fail to protect against challenge infections.

Animals↗
PubMed1984

A collaborative study of patient-initiated treatment of recurrent genital herpes with topical acyclovir or placebo.

Patient-initiated treatment of recurrent genital herpes with topical acyclovir was compared with placebo treatment in a multicenter collaborative trial involving 309 patients. No differences were found between the group using acyclovir and that using placebo except that herpes simplex virus was excreted for a shorter period by women using acyclovir. This difference was partially accounted for by the fact that some patients whose viral culture results subsequently proved positive began to use their medication before lesions formed. One hundred patients initially applied ointment within 6 hr of onset of the prodrome and before actual lesion formation. Separate analysis of this group showed a diminished duration of viral excretion by women using acyclovir and a reduced interval between lesion formation and total crusting in men using acyclovir, but both differences were of only borderline significance (.05 less than P less than .10). The results indicate that patient-initiated therapy with topical acyclovir in polyethylene glycol exerts no clinically significant effect on recurrent genital herpes.

Acyclovir↗
PubMed1984

Effect of eight antiviral drugs on the reactivation of herpes simplex virus in explant cultures of latently infected mouse trigeminal ganglia.

The effect of several antiviral drugs on the reactivation of herpes simplex virus type 1 in explant cultures of latently infected mouse trigeminal ganglia was investigated. Phosphonoacetate and phosphonoformate, which act directly on the virus-induced DNA polymerase, require a drug concentration of 400 micrograms/ml for the inhibition of virus reactivation in latently infected ganglia. Arabinosyladenine and arabinosyladenine monophosphate, which are phosphorylated to triphosphates by cellular enzymes and inhibit virus synthesis either by blocking the DNA polymerase or by incorporation into viral DNA, require a concentration of only 100 micrograms/ml for the inhibition of the reactivation process. Drugs that are phosphorylated by the virus-induced thymidine kinase, such as acyclovir, arabinosylthymine, bromovinyldeoxyuridine, and three fluorinated pyrimidine nucleosides require the lowest drug concentrations for complete inhibition of virus reactivation in latently infected ganglia explant cultures. Our data suggest that the inhibition of virus reactivation is dependent not only on drug concentration, but also on the number of latently infected neurons in the ganglia.

Acyclovir↗
PubMed1984

Effects of topical applications of phosphonoacetate on colonization of mouse trigeminal ganglia with herpes simplex virus type 1.

The effects of topical application of phosphonoacetic acid on the colonization of mouse trigeminal ganglia by herpes simplex virus type 1 were examined. The results showed that the extent of colonization of ganglia by virus is related to the time elapsed between virus inoculation and application of this agent. In most cases, treatment started up to 12 h after inoculation prevented invasion of ganglia by virus. When started up to 24 h after inoculation, treatment reduced and stabilized the amount of virus detectable in trigeminal ganglia during the acute phase of the ganglionic infection. Treatments started 24 h after virus inoculation had little influence on total virus accumulations in trigeminal ganglia. The data also indicate that virus titers in specimens of inoculated and treated skin sites are less affected by topical phosphonoacetic acid treatment than virus titers in ganglia. The experiments may represent a model system for testing effects of other antiviral compounds on colonization of ganglia by virus and may provide some clues regarding the pathogenic mechanism of herpes simplex virus infections.

Administration, Topical↗
PubMed1984

Kaposi's sarcoma in homosexual men. A seroepidemiologic case-control study.

The cases of 20 male homosexuals with Kaposi's sarcoma and the acquired immunodeficiency syndrome were compared with those of 40 age- and race-matched male homosexual controls. Patients with Kaposi's sarcoma had lower OKT4/OKT8 (T-helper/T-suppressor) ratios than controls, due to smaller numbers of OKT4 cells. Serum IgG concentrations and antibody titers to cytomegalovirus in patients exceeded those in controls, but patients had lower antibody titers to Epstein-Barr virus. Logistic regression analysis comparing patients with controls showed significant relative risks for Kaposi's sarcoma associated with the number of partners per month in receptive anal-genital intercourse, occasions per month of " fisting ," and cytomegalovirus antibody titers. Cytomegalovirus titers also were inversely correlated with OKT4 cell concentrations in the control group. Significantly greater OKT4 cell concentrations were found at diagnosis in HLA-DR5-positive patients than in HLA-DR5-negative patients. Patients who have HLA-DR5 may express disease at lesser degrees of immunodeficiency than HLA-DR5-negative patients.

Adult↗
PubMed1983

Dissemination of herpes simplex virus in ganglia after footpad inoculation in neurectomized and non-neurectomized mice.

After unilateral footpad inoculation with herpes simplex virus (HSV) the infection spreads initially to the ipsilateral and afterwards to the contralateral spinal ganglia. In about 25 percent of the mice the virus also reaches the trigeminal ganglia. Furthermore, we have shown that only a complete severance of the nervous connections can prevent the colonization of ganglia with HSV after footpad inoculation. Results of previous experiments in which only the sectioning of the sciatic nerve was able to prevent the invasion of ganglia, are difficult to explain. It appears also that HSV travels in the nerve toward the ganglia in a non-infectious form, and that the infectious virus detectable in nerves originates not from the peripheral inoculation site, but from the infectious virus pool which accumulates in spinal ganglia. A limited role of the circulatory system in the colonization of sensory ganglia by HSV cannot be excluded, since in a few cases virus was detected in ganglia after sectioning of both the sciatic and the femoral nerve.

Animals↗
PubMed1983

Effect of discontinuous acyclovir treatment on in vitro reactivation of herpes simplex virus from latently infected trigeminal ganglia.

Exposing explant cultures of latently infected mouse trigeminal ganglia alternately to acyclovir-containing and drug-free medium led to a significant decrease in the proportion of ganglia containing reactivatable herpes simplex virus. The loss of virus from the explant cultures was not caused by thermal inactivation during prolonged incubation periods. The efficiency of virus elimination may depend on the frequency and duration of the alternating treatment and on the number of latently infected neurons in the ganglia.

Acyclovir↗
PubMed1982

Treatment of experimental latent herpes simplex virus infections with acyclovir and other antiviral compounds.

Acyclovir can prevent the establishment of latent herpes simplex virus (HSV) in sensory ganglia by early treatment of the primary infection in experimental animals. A delayed treatment may reduce the number of neurons that eventually become latently infected. Acyclovir can prevent virus reactivation in explant cultures of latently infected ganglia, experimentally induced recurrences of latently infected animals, and immunosuppressed patients. This effect is dependent on the continuous presence of the drug in the explant culture medium or organism. The treatment of recurrent lesions with acyclovir reduces the severity of the episode and may also prevent reinfection of ganglia, if this should be common in the maintenance of latency. It might be possible to eradicate a latent HSV, if conditions were created in which drugs such as acyclovir, activated by the virus-induced thymidine kinase, could interact with the enzyme before the assembly of mature virions.

Acyclovir↗
PubMed1982

The prevalence of neural tube defects among ethnic groups in Brooklyn, New York.

Records of almost 174,000 consecutive births at six Brooklyn hospitals during the years 1968-1976 were reviewed for congenital neural tube defects. Prevalence of anencephaly, myelomeningocele and occipital encephalocele combined was significantly higher in infants delivered to mothers born in Puerto Rico than in offspring of non-Puerto Rican whites or blacks. The association of prevalence rates with ethnicity remained significant after adjustment for several variables. However, when adjustment was made for private or service status the difference between Puerto Ricans and whites, although still appreciable, was no longer statistically significant. No significant differences in prevalence rates between whites and blacks were observed. Sex ratios of affected infants were close to unity in each ethnic group. Statistically significant associations were found between the prevalence of neural tube defects and parity, gravidity and economic status. The patterns of these associations varied among the ethnic groups. A declining trend in the prevalence of myelomeningocele was observed for all ethnic groups.

Black People↗
PubMed1982

Arabinosyladenine monophosphate in genital herpes: a double-blind, placebo-controlled study.

A double-blind, placebo-controlled study was performed in 55 male patients with recurrent herpes simplex genitalis. The 29 patients who received topical arabinosyladenine monophosphate (ara-AMP) showed no significant difference in viral shedding, duration of pain, healing time or development of new lesions as compared to 26 placebo-treated patients. Ara-AMP was well-tolerated when topically applied. Serum neutralizing antibody titers did not change significantly during the acute and convalescent periods of the patient's recurrent HSG attacks. We conclude that ara-AMP, when applied topically as a 10% gel five times a day within 24 h of onset of recurrent HSG, does not influence the virologic and clinical evolution of the recurrent episode.

Administration, Topical↗
PubMed1982

Failure of 2-deoxy-D-glucose in the treatment of experimental cutaneous and genital infections due to herpes simplex virus.

The effectiveness of 2-deoxy-D-glucose (2-DG) was evaluated in the treatment of cutaneous infections with herpes simplex virus type 1 (HSV-1) in mice and genital infections with HSV type 2 (HSV-2) in mice and guinea pigs. Groups of mice were inoculated in the lumbosacral or orofacial area with HSV-1 and treated topically three times a day with 0.2% or 0.5% 2-DG solution beginning 3 hr after inoculation. No effect on skin lesions, mortality, or latency was observed. Mice were inoculated intravaginally with HSV-2 and treated intravaginally three times a day with 0.2%-5% 2-DG in solution or suspended in miconazole nitrate cream beginning 6 hr, 24 hr, or 48 hr after inoculation. Replication of HSV-2 in the vagina and final mortality were not affected. Guinea pigs were infected intravaginally with HSV-2 and treated both intravaginally and topically on the external genitalia four times a day with 1% or 5% 2-DG in miconazole nitrate cream. Treatment initiated just prior to development of lesions (on day 3 after inoculation) did not alter vaginal virus replication, lesion development and severity, or virus titers in lesions.

Administration, Topical↗