Search

Forward head and shoulder postures and associated muscle imbalances are prevalent among today's workers, according to ongoing research in the physical therapy field. Information on proper posture should be used proactively to educate employees as part of injury prevention training. Maintaining muscle strength in the desirable posture will require ongoing exercise and attention from the worker. The self-direct approach will not eliminate all cases of tendonitis, epicondylitis and other disorders, but it will have a significant positive impact.

Acute hemorrhagic conjunctivitis, an infection caused by enterovirus 70 and a variant of coxsackievirus A24, is characterized by the rapid onset of severely painful conjunctivitis and subconjunctival hemorrhage. The condition is usually benign and resolves in five to seven days; however, a polio-like paralysis (radiculomyelitis) develops in approximately one in 10,000 patients infected with enterovirus 70. No treatment is available. Information about acute hemorrhagic conjunctivitis should be provided to patients and the community in order to prevent undue alarm, discourage home remedies and control the spread of this highly contagious disease.

We investigated the protective effects of combinations of interferon-alpha (IFN-alpha) and neutralizing monoclonal antibodies (mAbs) and serum antibodies against poliovirus type 1 (PV-1) in vitro. Our results indicate that the antiviral effects of IFN-alpha and most neutralizing mAbs to PV-1 act synergistically to inhibit PV-1. However, the antiviral effects of IFN-alpha and one type specific mAb to PV-1 were additive. Further, the protective effects observed with combinations of IFN-alpha and rabbit, monkey or human serum containing effects observed with combinations strains Mahoney (Mah) and Sabin (Sab) were similar to those observed with combinations of IFN-alpha and mixtures of mAbs with synergistic and additive activities. Our studies suggest that the antiviral activity of neutralizing antibody acts with the antiviral activity of IFN to inhibit virus infection synergistically or additively and that the different antibody activities are associated with the mechanism of neutralization.

A spectrophotometric assay is described for the detection of interferon (IFN) dependent antibody (IDA) activity (i.e., antibodies that act with IFN to synergistically inhibit virus infection) and IFN independent antibody (IIA) activity (i.e., antibodies that act additively with IFN to inhibit virus infection). Four neutralizing monoclonal antibodies (mAb) against poliovirus type 1 (PV-1) were tested. Three mAb exhibited IDA activity and one mAb exhibited IIA activity against PV-1 strain Sabin. Concomitantly, the respective IDA and IIA activities were confirmed by a yield reduction assay. Also, the spectrophotometric assay detected IIA activity against PV-1 and IDA activity against PV-2 and PV-3 in human serum. Interestingly, antibody to a synthetic peptide of PV-1 capsid protein VP2 exhibited IIA activity against PV-2 strain MEF. Thus, this assay can facilitate the identification and investigation of IDA and IIA activities. Further, the assay adds economic feasibility to studying the natural occurrence of these antibody activities in the general population and can be useful in assessing the therapeutic potential of vaccine induced and hyperimmune antibodies.

The antiviral activity of cell-associated, non-elutable recombinant human gamma interferon (rHuIFN-gamma) was neutralized by antibody. The neutralization of cell-associated rHuIFN-gamma was maximal through 2 h (60-100%) and declined through 8 h (20-40%). Concomitantly, the antiviral activity of cell-associated [Met-Gln-Asp-Pro]-rHuIFN-gamma was sensitive to trypsin digestion over the same time period. However, the cell-associated antiviral activity of [Cys-Tyr-Cys]-rHuIFN-gamma remained sensitive to trypsin through 8 h. Neutralization of cell-associated rHuIFN-gamma by antibodies to the N-terminal end of HuIFN-gamma suggests that the N-terminal end(s) of cell-associated rHuIFN-gamma is directed outward from the receptor. Further, immunoprecipitation of radio-labelled rHuIFN-gamma by antibody alone suggests that biologically active rHuIFN-gamma is an oligomer. Taken together, these studies suggest that neutralization of cell-associated rHuIFN-gamma is probably due to divalent binding of antibody to or between rHuIFN-gamma in receptors on the cell surface. Also, our studies indicate that rHuIFN-gamma can remain associated with the cell surface during the induction of the antiviral state (AVS) and that binding of antibody to cell-associated rHuIFN-gamma inhibits the molecular events responsible for induction of the AVS.

Twenty-eight severely mentally ill adults in an inner-city area of Atlanta participated in a study to determine if intensive outreach by case managers would result in decreased use of mental hospitals and improved community living. The experimental group of 14 clients received intensive support from case managers in the community who helped them anticipate and prevent crises, maintain medication schedules, and address problems in living. Fourteen clients in the control group received some of these same services but at a less intensive level and only at the offices of the case managers. Compared with control clients, experimental clients had an average of ten fewer hospital days and better adherence to medication regimens and agreed-upon service plans during the project.

The first part of this paper describes the nature of a Moot Court (or Mock Trial) and how it has been used in recent years as a teaching method for students in medicine and nursing at the Memorial University of Newfoundland. A whole day is spent in the enactment of an imaginary court case in which issues in bioethics are raised. Civil and criminal cases are used in alternate years. A considerable degree of realism is maintained except for the occasions when the presiding judge needs to make comments to the students in order to explain what is going on. The realism is helped by the fact that the roles of judge and of legal counsel are played by members of the judiciary and lawyers from the Newfoundland bar. In the second part of the paper there is a discussion of the principal issue that arose in the 1988 Moot Court, namely informed consent. In the third part the secondary legal and moral issues that arose are described and in the fourth part there is a discussion of the interface between law and morality that is illustrated by the issues that came up in the Moot Court.

Acute hemorrhagic conjunctivitis (AHC) viruses--enterovirus type 70 (E70), and coxsackie-virus type A24 (CA24)--infect the superficial cells of the conjunctiva and cornea. We examined the growth of several E70 and CA24 isolates in monkey, rabbit, and mouse conjunctival and corneal (C/C) cells. We found that E70 isolates grew well in monkey (10(6.5) TCID50/ml), rabbit (10(4.5) to 10(5.5) TCID50/ml), and mouse (10(3.5) to 10(6.0) TCID50/ml) C/C cultures and caused cytopathic effects (CPE). In contrast, CA24 isolates replicated well and caused CPE only in monkey C/C cultures (10(6.5) TCID50/ml). These results show that E70 isolates grow readily in monkey, rabbit, and mouse C/C cells whereas CA24 isolates replicated in monkey C/C cells only. This finding is consistent with the suggestion that a lower animal reservoir may be a source of human infection by E70. These cell culture systems may be useful for studying virus-cell interactions and host defenses operating at the surface of the eye and for evaluating the feasibility of prophylactic or therapeutic use of interferon, interferon inducers, and/or antibody for controlling AHC virus infections.

Virus-specific, early appearing neutralizing activities (ENA) and interferon (IFN) were detected in tears collected from patients during epidemics of acute hemorrhagic conjunctivitis (AHC). In one study, ENA that neutralized enterovirus type 70 (EV70) was detected in tears collected from 114 of 130 AHC patients in Florida. In another study, ENA against coxsackievirus type A24 (CA24) was detected in tears collected from 39 of 57 patients in Singapore with AHC caused by CA24. No tear samples contained ENAs to both EV70 and CA24. Tear samples from uninfected eyes did not contain ENA to EV70 or CA24. ENA to EV70 was detected in 6 of 11 patients 1-6h before the onset of AHC. In addition, tears of 68% of patients seen on the day of onset produced tears that contained ENA to EV70. Thus, ENA to EV70 may be detected less than 24h after infection (based on 24h incubation period). IFN beta was detected in 30% of tear samples collected from patients on the day of onset of AHC caused by EV70. This finding suggested that ENA and IFN could act together to inhibit primary infections of AHC. It was found that the combination of ENA and IFN inhibited virus replication synergistically (greater than or equal to 300 fold reduction) in preinfected cells. Our findings suggest that ENA represents a previously unreported early defense mechanism of the eye, that endogenous ENA and endogenous IFN could inhibit viruses synergistically in vivo, and that ENA in tears could be useful in identifying the agent causing AHC.

Two Navajo Indian children with severe combined immunodeficiency disease (SCID) lost reconstituted immune function after virus infections. A serum factor which inhibited normal lymphocyte response to mitogens was found in one of them and led to the examination of sera from five other Navajos with SCID. Mean inhibition by six Navajo sera was 67%; no inhibitor was found in sera from normal adults and children. The inhibitor activity was nondialyzable and heat stable, yet partially sensitive to pH 2.0, suggesting that interferon(s) was present. Interferon (IFN) activity in patient sera ranged from 10 to 300 U/ml. Normal children had peak serum IFN levels of 100 and 30 U/ml in the acute and convalescent periods, respectively, of virus infections. IFN alpha, IFN beta, and IFN gamma were identified in SCID sera by specific antisera. Both inhibitor and IFN activities in three Navajo sera were 88-95 and 89-100%, respectively, removed with anti-IFN antisera. Similar patterns of inhibition of lymphoblastogenesis were seen with IFN standards. IFN levels in the SCID patients did not correlate with documented infections; elevated levels were present when no infections could be documented. The immunologic imbalances in some forms of SCID may be related to circulating inhibitors, possibly interferon.

Previous studies have demonstrated the importance of IFN alpha/beta in resistance to primary viral infections. However, the role of IFN gamma in primary infections is unclear. The present studies were undertaken to determine whether IFN gamma induction was an important early host defense against primary HSV infection. The approach was to block the IFN gamma response with antibodies to IFN gamma prior to infection and at various times post-infection (p.i.). The data indicates that treatment of mice with anti-IFN gamma prior to infection enhanced mortality (89% vs 37%). Anti-IFNs given at various times post HSV challenge proved most effective within the first 24 h of infection. The above results suggest for the first time that IFN gamma mediates important host defense(s) early during primary HSV infection. Similar results were obtained using antibody to IFN alpha/beta.

Antibodies to an N-terminal synthetic peptide of mouse gamma interferon (MoIFN gamma) neutralized the antiviral activity of MoIFN gamma but not MoIFN alpha/beta, human IFN alpha (HuIFN alpha), HuIFN beta or cynomologus monkey IFN gamma (CynIFN gamma). Comparatively, antibodies to mouse N-terminal synthetic peptide showed only 10% reciprocal cross-reactivity in neutralization tests against heterologous HuIFN gamma and 13% cross-reactivity in the ELISA test against Hu N-terminal peptide. The predetermined specificity of these antibodies make them powerful tools for studying antigenic relatedness and biological properties of IFN gamma s.

Antibodies to a synthetic carboxy-terminal peptide (Cys-Ser-Leu-Arg-Lys-Arg-Lys-Arg-Ser-Arg-Abu) (gamma-C-TP) of mouse interferon-gamma (MuIFN-gamma) were produced in rabbits. They neutralized the antiviral activity of MuIFN-gamma but not that of MuIFN-alpha/beta or human (Hu) IFN-alpha/beta or -gamma. They also inhibited the IFN-dependent enhancement of natural cytotoxic cells (NCC) and the in vivo plaque-forming cell (PFC) response to sheep red blood cells (SRBC). Thus, our results indicate that polyclonal antibodies specific for the nine carboxy-terminal amino acids of MuIFN-gamma can specifically inhibit the antiviral and immunoregulatory activities of this IFN in vitro. In addition, our findings indicate that endogenous production of MuIFN-gamma in vivo plays a role in development of the full antibody response to SRBC surface antigens.

Natural human interferons (IFN) and recombinant human IFNs (rIFN-alpha and rIFN-beta) inhibited the production of virus in Chang's human conjunctival cell cultures infected with epidemic isolates of acute hemorrhagic conjunctivitis virus, Coxsackievirus type A 24 (CA24). Generally, natural and rIFN-alpha and rIFN-beta were equally effective in inhibiting CA24 infection. However, rIFN-alpha A was more effective than rIFN-alpha C, D, I, J, and K in reducing virus infection, cytopathogenesis, and virus production. Recombinant IFN-alpha J was least effective in inhibiting CA24 in human conjunctival cell cultures. Also, the IFN titer was reduced 10- to 1,000-fold when cells were infected with greater than or equal to 0.3-0.5 CA24/cell, suggesting a dose-dependent IFN resistance by CA24. These results suggest that the antiviral activity of IFN against acute hemorrhagic conjunctivitis in vivo may vary with the CA24 isolates, the MOI, the type of IFN, and the time of infection with respect to beginning IFN treatment.

Interferon is established as one of the natural defenses against virus infection. The evidence that interferon may serve a defensive role against certain protozoa is less complete and consists mainly of induction of interferon during protozoal infection, as well as interferon protection of mice against malarial infection. The evidence that interferon may function as a defense against certain bacterial infections is extended with data indicating that a wide variety of bacteria can induce interferon in the mouse and in cultured human peripheral lymphoid cells. This induction of interferon by bacteria and the ability of interferon under many conditions to activate neutrophils and macrophages raises the possibility that interferon may serve a defensive role against some bacteria.

We developed a fixed-volume porcine hemorrhage model that simulates the rapid exsanguination of combat or civilian trauma victims. In this study we compared the ability of colloid resuscitation solutions to prevent death after an otherwise lethal hemorrhage in 100 swine. The shed blood was replaced in a 1:1 ratio with either autologous whole blood (WB), untyped swine fresh frozen plasma (FFP), typed FFP, 5% human serum albumin (ALB), or normal saline (NS). Survival rate analysis indicated that WB was significantly better than FFP (untyped), ALB, or NS but not better than typed FFP. The 24-hour survival rates were: WB = 90%, typed FFP = 79%, untyped FFP = 56%, ALB = 57%, and NS = 25%. All deaths in the untyped FFP group suddenly occurred during or within 15 minutes after treatment in a recovering animal. Deaths in the ALB group steadily occurred for up to 2 1/2 hours after treatment. Analysis of hemodynamic, arterial blood gas, and acid-base data indicated that WB and FFP provided a better acid-buffering capacity in surviving animals than NS or ALB. We conclude that compatible FFP is a better resuscitation agent than ALB after an otherwise fatal hemorrhage because FFP is a better acid buffer.

Human stomach adenocarcinoma (AGS), astrocytoma (AST) and myelogenous leukemia (K562) cells were co-cultured with human peripheral blood leukocytes (PBL) through four days. Histamine releasing activity (HRA, lymphokines that stimulate degranulation of basophilic leukocytes with the release of histamine) and interferons alpha and gamma (IFN alpha and IFN gamma) were detected in the culture fluids. Maximal levels of HRA were detected by 24 hr in AST and K562-leukocyte co-culture fluids. Notably, only low levels of HRA was detected in AGS-leukocyte cultures. HRA was separated into two molecular weight species (60,000 and 25,000) by column chromatography. The IFN activity was shown to be a mixture of IFN alpha and IFN gamma (IFN alpha greater than IFN gamma). IFN did not cause histamine release from human PBL or affect HRA. Our results indicate that PBL from normal individuals produce HRA in response to tumor antigen and suggest that the basophilic leukocyte response to certain cancers may be related to HRA production.

Previous studies with the lymphokine, histamine-releasing activity (HRA), showed that HRA consisted of a heterogeneous group of molecules. The possibility of using thoracic duct lymphocytes (TDL) as a source of large quantities of HRA has been investigated. Antigen-stimulated TDL synthesize and release HRA in quantities similar to an equivalent number of peripheral blood lymphocytes (PBL). Streptokinase (SK) antigen routinely caused TDL to produce HRA approximately 15,000 Da. In contrast, staphylococcus enterotoxin B (SEB) induced the formation of a heterogeneous mixture of HRAs with apparent molecular weights of 50,000 and 15,000. Two peaks of activity (HRA I and II) were recovered when the supernatant from SK-stimulated TDL was subjected to ion-exchange chromatography. Interestingly, basophil chemotactic activity (BCA) was also eluted in these two peaks. Although interferon (IFN) is also released by antigen-stimulated TDL, the nonidentity of IFN and HRA was established by fundamental differences in chromatographic properties and specific antisera to IFN. In contrast, these studies suggest that HRA and BCA may be present on the same molecular entity.

The virulence of a herpes simplex virus type 2 (HSV-2) isolated from the urine of a patient (SL) with acquired immunodeficiency syndrome (AIDS) and bilateral acute retinal necrosis (ARN), was investigated in mice. The ratio of plaque forming units (PFU) in fibroblasts to the 50% lethal dose (LD50) of HSV-2(SL) in mice was 10 fold more than the PFU to LD50 ratio of a neurovirulent HSV-2, strain 186. Further, HSV-2(SL) caused retinitis with and without lethal encephalitis in mice inoculated intracranially (i.c.). In contrast, mice inoculated with HSV-2(186) died of encephalitis without ocular disease. HSV-2(SL) was isolated from eye and/or brain tissue 1 to 15 days post i.c. inoculation. Ocular disease progressed from an initial mild chorioretinitis on day 8 to total retinal necrosis with panuveitis by day 11 in mice given 10 PFU of HSV-2(SL) i.c. HSV antigen was detected initially in the cells of the optic nerve and spread into the ganglial cells of the nerve fiber layer, the neurosensory cells of the inner nuclear layer, and the cells of the retinal pigment epithelium (RPE) between days 8 and 10. Thus, this study supports the concept that HSV neurovirulence varies between strains and presents a HSV-2 neurotransmission animal model of ARN.

Protein A from Staphylococcus aureus (SpA) has been observed to stimulate the production of human gamma interferon (HuIFN gamma) by peripheral blood mononuclear cells (MNC). Dose-dependent experiments showed donor-to-donor variation in the concentration of SpA required for maximum IFN production although 50 micrograms/ml consistently produced near peak IFN gamma titers for each donor. Kinetic studies revealed that peak IFN gamma production occurred 24 hr after SpA stimulation. Physicochemical and antigenic characterization showed that SpA-induced IFN possessed the characteristics of IFN gamma in that it was inactivated by treatment at pH 2, heating at 56 C and anti-HuIFN gamma serum but not by anti-HuIFN alpha serum. Further studies showed tha maximum IFN gamma production could be achieved by stimulating 5 x 10(6) MNC/ml and IFN gamma could be harvested for 3 successive days by removing IFN gamma-containing supernatant fluids and adding fresh medium to stimulated MNC cultures. Preliminary cell fractionation studies suggest that the mononuclear cell that produces IFN gamma after SpA stimulation is a nonadherent lymphocyte that lacks high affinity receptors for sheep erythrocytes and expresses Fc receptors for IgG. Moreover, unlike other mitogen inducers, SpA appears to be less dependent on the presence of macrophages for IFN gamma production.

Three children and one adult with chronic mucocutaneous candidosis with documented deficient cellular immunity to Candida antigen were evaluated as a model to study the specific cellular immune-enhancing potential of the prostaglandin synthetase inhibitor ibuprofen. Oral ibuprofen failed to have any consistent effect during sequential 4-week on and off cycles on the following parameters: delayed hypersensitivity skin testing; lymphocyte transformation to Candida antigen; T-cell subsets as determined by monoclonal antibody techniques; production of human immune interferon in response to staphylococcal enterotoxin A (SEA). Two patients showed a trend toward enhanced lymphocyte transformation to PHA while taking ibuprofen. In two patients who were studied 8-10 weeks after discontinuation of oral ketoconazole therapy, clinical recurrence of CMC was not prevented by oral ibuprofen therapy.

An epidemic of acute hemorrhagic conjunctivitis in Miami, Florida, involved approximately 800 documented cases and more than 2,500 suspected cases. This epidemic was caused by an enterovirus 70 infection affecting primarily young black people residing within a high-risk area. Acute hemorrhagic conjunctivitis is characterized by the rapid onset of swollen eyelids, foreign-body sensation, burning, watery discharge, and, usually, bilateral ocular involvement. Signs include distinctive bulbar conjunctival hemorrhages and a follicular conjunctival reaction with only mild and infrequent corneal involvement. This infection is short in duration, self-limited, and free of significant ocular sequelae. Symptomatic treatment appears to be as effective as various topical medical regimens for relief of symptoms. Secondary bacterial infections (occurring in individuals who used urine as an eyewash) and one case of a transient acute Bell's palsy were the only complications associated with this acute hemorrhagic conjunctivitis epidemic.

A rabbit enterovirus 70 (EV70) model infection that closely mimics human enteroviral conjunctivitis was developed. Conjunctivitis occurred 24 hr following topical application of EV70. The conjunctivitis was characterized by tearing, redness, swelling of the eye lids, follicles in the superior palpebral conjunctiva, and dilatation of subconjunctival blood vessels. Histologic examination of conjunctival and corneal tissue taken 1 and 2 days after infection revealed numerous punctate areas devoid of squamous epithelium on the upper palpebral conjunctiva. Also, follicles without germinal centers were observed microscopically in the palpebral and tarsal conjunctiva. Fibroblast infiltration characteristic of wound healing and a sparse mononuclear infiltration was noted by the second day. Peak levels of virus [10(3) to 10(6.2) plaque forming units (PFU)/ml] were detected 1 to 2 days after infection and declined to undetectable levels after 3 to 5 days. Interestingly, antiserum to parental EV70 was less effective (8-10-fold) in neutralizing EV70 adapted to animal and tissue culture systems. This finding suggests that an antigenic variant of EV70 arose during adaptation. Fibroblast interferon (IFN beta), which is indicative of viral infection, was detected in tears from 6 of 16 rabbits and declined to undetectable levels 3 days after infection. Serum antibody to EV70 was detectable 8 to 10 days after infection. However, the level of serum antibody was highly variable. The results indicate that the clinical disease, virologic and immunologic courses were similar to that of the human infection. Results suggest that this animal model provides a system for studying the natural antigenic variation of EV70, the natural host defenses of the eye, and antiviral treatments against enteroviral conjunctivitis.

Enriched human B lymphocytes cocultivated with mouse L cells produced human leukocyte interferon (IFN-alpha) and shortly thereafter transferred antiviral activity to the recipient cells (99% inhibition of expected virus yield). In contrast, cocultivation of enriched T-cell populations with mouse L cells resulted in no IFN production or transfer of antiviral activity. In addition, both T and B lymphocytes pretreated with exogenous IFN or stimulated in vitro by mitogens could transfer antiviral activity to human WISH cells. The transfer of antiviral activity was not blocked by antibodies to IFN. The data indicate that both T and B cells can be recruited by IFN to transfer antiviral activity. Thus, once cells are recruited by IFN they can transfer antiviral activity in the absence of IFN and protect cells locally or distally from the site of infection.

The possibility that interferon (IFN) and antibody could act together to reduce virus yields in infected cells was suggested by the simultaneous occurrence of IFN and antibody at infected sites. In the present in vitro studies, mixtures of IFNs and antibody acted synergistically to reduce virus yields in cultures infected with coxsackievirus A24, enterovirus 70, adenovirus, and herpes simplex virus. This synergistic reduction was observed in different cells and at different concentration of IFN and antibody. Although IFN and antibody acted synergistically against all viruses tested, the degree of synergism was dependent on the type of IFN or the virus. For example, IFN-beta and antibody was 10 to 200 times more effective than IFN-gamma and antibody against coxsackievirus A24, enterovirus 70, and adenovirus. A combination of antibody and IFN-gamma was three to five times more effective than IFN-beta and antibody against herpes simplex virus. In addition, we found that endogenously produced IFN-beta could act synergistically with antibody to coxsackievirus A24 to increase the overall antiviral effect by 10(5.0)-fold. No effect of endogenous IFN was observed in herpes simplex virus-infected cultures treated with antibody to herpes simplex virus. These studies indicate the potential importance of the synergistic effect of locally produced IFN and antibody in restricting virus early in the natural infectious process. They also suggest that combinations of IFNs and antibody may be more beneficial in the treatment of certain virus infections than IFN or antibody alone.

Some evidence indicates that ibuprofen and other prostaglandin synthetase inhibitors may have the potential for cellular immune enhancement in addition to their anti-inflammatory activity. If this is true, treatment of rheumatoid arthritis, a disorder of presumed autoimmune pathogenesis, would present a dilemma. These agents are widely used in rheumatoid arthritis for their anti-inflammatory effects. If they are found to enhance cellular immune function, however, the disease might be stimulated over the long term, rather than suppressed. Preliminary evidence from four patients with rheumatoid arthritis show that oral ibuprofen had no significant immunologic effect during sequential "on" and "off" cycles, as assessed by the following measures: delayed hypersensitivity skin testing; lymphocyte transformation to mitogen (phytohemagglutinin) or specific antigen (Candida albicans); T-cell subsets, as determined by monoclonal antibody techniques; or production of the lymphokine, human immune interferon, in response to phytohemagglutinin or to staphylococcal enterotoxin A. Early evidence, therefore, suggests that oral ibuprofen therapy may be 'immunologically safe' in patients with rheumatoid arthritis, but investigations of large series of patients also assessing local immune reaction in diseased joints may be necessary for confirmation.

The clinical, virological, and immunological courses of a laboratory-acquired hemorrhagic conjunctivitis were followed. Coxsackievirus type A24 (CA24) was isolated from tears for only two days but from sputum and fecal samples for 20 days. Maximal levels of virus were detected in the right eye (10(5.1) 50% tissue culture infective doses/ml) 5-7 hr before conjunctivitis in the right eye, and in feces (10(2.8) 50% tissue culture infective doses/g) and sputum (10(2.5) 50% tissue culture infective doses/ml) five and eight days after onset of conjunctivitis, respectively. Specific neutralizing activity against CA24 was detected in tear samples 48-56 hr after exposure, and elimination of virus was associated with the rise in the neutralizing activity in tears. This activity was detected earlier than previously reported antibody responses of the eye. The absence of interferon and the association of this early neutralizing activity in tears with early elimination of virus from the eye suggest that neutralizing activity may play a major role in the clinical and pathological manifestations of this infection.

Nonsensitized human leukocytes cocultured with various xenogeneic epithelioid and fibroblastic cells produced human leukocyte interferon and shortly thereafter transferred antiviral activity to the xenogeneic cells. Antiviral activity in the cocultured xenogeneic cells was not due to cell-mediated cytotoxicity as measured by specific 51Cr release and staining with vital dyes. The transfer of antiviral activity from leukocytes to xenogeneic cells was blocked by rabbit antiserum to human leukocyte interferon. Transferred viral resistance failed to develop in actinomycin D-treated xenogeneic cells, even though these cells induced human leukocyte interferon. Based on these findings, it appears that interferon made in the cocultures acts on the leukocytes to effect the transfer of interferon-induced viral resistance to the xenogenic cells, possibly by transmission of an inducer for the antiviral state. These studies strongly suggest a new and efficient host defense against virus infection which does not require killing of noninfected or recently infected cells.