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A controlled serologic survey of antibody titres to 17 viruses was undertaken in multiple sclerosis patients in the Orkney and Shetland Islands. No consistent pattern of elevated antibody titre levels or the presence of antibody was noted in patients compared with two control groups. Because of the isolation of these islands, the mean age at acquisition of common childhood infections, including measles, was considerably older than that of inhabitants of Europe and the United States of America. The age of occurrence of varicella was consistently younger in patients than in controls. Of note is the fact that six patients had measles after the onset of MS. This study failed to incriminate any of the viruses tested in the aetiology of MS.

Neurologic disease occurs frequently in patients infected with the human immunodeficiency virus (HIV), and a large body of literature now exists detailing the various infections, neoplasms, and other conditions that can affect the central nervous system (CNS) or the peripheral nervous system in children and adults with AIDS, persistent generalized lymphadenopathy, or (in some cases) only serologic evidence of retroviral infection. Although certain opportunistic infections (toxoplasmosis, cryptococcosis, progressive multifocal leukoencephalopathy, and herpesviral infections) and CNS lymphomas often produce CNS disease in patients with AIDS, it is now clear that many cases of neurologic disease are caused by a group of disorders thought to be related to direct CNS infection by the AIDS retrovirus. Disease of the peripheral nervous system is also being increasingly recognized; some cases probably have an autoimmune basis.

The enzyme-linked immunosorbent assay (ELISA) was used to determine levels of specific IgG antibodies against measles, rubella, vaccinia, corona (OC43) and mumps viruses in cerebrospinal fluid (CSF) and serum of 18 patients with clinically definite multiple sclerosis (MS), 8 patients with optic neuritis (ON), 27 patients with other neurological disease (OND), and 88 control subjects without central nervous system disease. Serum antibody levels were not significantly different between the four groups. Differences in the frequency and levels of CSF antibodies between the four groups were observed. Control patients had serum/CSF antibody ratios from 2.0 to 3.0 (log) with an average of 2.5 corresponding to a 320-fold difference between serum and CSF antibody levels. MS patients had ratios from 1.1 to 2.1 with an average of 1.6. The average was 2.0 for the ON patients. The average for the OND patients was similar to the controls. The altered serum/CSF ratios for several viruses within an individual patient was similar. These results suggest that nonspecific immunostimulation is responsible for the increased levels of CSF virus antibodies.

Antibodies against herpes simplex virus (HSV) types 1 and 2 and cytomegalovirus (CMV) were assayed with a microindirect hemagglutination (IHA) test in the serum of 67 pairs of patients with Parkinson's disease and controls. Cerebrospinal fluid from 30 pairs was assayed. All patient and control serum was tested with a radioimmunoassay (RIA) for antibodies against HSV type 1 subunit antigens. Serum IHA antibody level against HSV type 1 was increased in patients with Parkinson's disease and RIA antibody levels against the same viral antigen were significantly higher in the patients than controls. Herpes simplex virus type 2 and CMV serum antibodies were equal in the patient and control groups. Most of the CSF samples tested negatively for IHA; small and comparable numbers of the patients and controls had low antibody levels against HSV and CMV antigens.

The incidence of clinical maternal infections was determined in a prospective study of 44,016 pregnant women at 12 university hospitals. Viral and bacterial infections were the most frequently reported. Overall, the highest incidence of infections was for vaginitis, influenza/"flu"-like disease, and infections of the kidney, ureter, bladder; parasitic and fungal infections occurred at low rates. Most women experienced only one infection during pregnancy (89.7%); however, some had two different infections (8.5%), and a few had three or more (1.7%). The analysis of the effects of some of the maternal infections on the pregnant women and their children have been published, and further studies are in progress.

Fetal rhesus monkeys were inoculated intracerebrally with an attenuated strain of western equine encephalitis virus. All animals developed microcephaly. Twelve of sixteen monkeys developed ex vacuo hydrocephalus. All virus inoculated fetuses developed WEE virus antibody. Virus could not be recovered at the time of delivery. Monkeys with the highest WEE antibody titers showed the greatest degree of hydrocephalus.

Genital herpes simplex virus infection in women was studied by using conventional tissue culture (TC) virus isolation compared with short-term (24-h) TC on Lab-Tek chamber slides followed by fluorescent-antibody (FA) staining. Three different staining techniques were used after TC: (i) staining with biotin-avidin (TC-BA/FA), (ii) direct FA (TC-FA), and (iii) indirect FA. The TC-BA/FA method showed complete correlation with the TC method. The TC-FA method showed no false-positive results but 31.5% false-negative results compared with the TC method. In contrast, the TC-indirect FA method showed 11.9% false-positive results and 11.7% false-negative results. The direct staining of specimens by the biotin-avidin technique (direct BA/FA) without prior tissue culture showed 37.7% false-positive results and 11.1% false-negative results. The TC-BA/FA technique thus was as sensitive as, but more rapid than, the TC method. The quality of fluorescence was far superior in TC-BA/FA staining as compared with TC-FA or TC-indirect FA procedures. The TC-BA/FA appears to be a valuable technique in laboratory diagnosis of genital herpes infections, especially in clinical situations requiring rapid detection of the virus.

Tropical spastic paraparesis (TSP), a chronic myelopathy of unknown etiology, was studied in the Seychelles. Human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus antibodies were determined using an enzyme-linked immunosorbent assay and confirmed with an indirect fluorescent antibody test in serum samples of 20 patients with TSP and 16 controls. Test results indicated that 17 patients (85%) and two controls (transverse myelopathy and clinically probable multiple sclerosis) were positive for HTLV-I. Serum samples of nine healthy controls and five with other neurologic diseases were negative for HTLV-I. No serum samples were positive for human immunodeficiency virus. Estimated relative risk for TSP in those subjects whose serum is positive for HTLV-I antibodies is 40. This result is highly statistically significant. Although primarily associated with adult T-cell leukemia and non-Hodgkin's lymphoma, HTLV-I could also be an etiologic agent of TSP.

HLA types and levels of humoral and cell-mediated immune responses to several antigens were studied in a large group of patients with multiple sclerosis, and in controls. Patients were more likely than controls to have the DRw2 antigen. They had higher mean antibody titers to measles but not to cytomegalovirus, herpes 1, or herpes 2, and had less competent cell-mediated responses. Antibody titers to measles were lower and cell-mediated immune responses were more effective in patients with the DRw2 antigen in patients than in patients without it. This apparent specificity for measles suggests that the etiology of multiple sclerosis is related to the immune response to measles or related viruses.

A new method for attaching antigens to latex by an avidin-biotin technique is described. The procedure permits control of the amount of antigen attached to the latex and eliminates the need for highly purified antigens and destructive bridging chemicals. The avidin-biotin latex agglutination assay is a simple, rapid test well suited to detection of viral antibody. The sensitivity and specificity, respectively, of the avidin-biotin latex agglutination assay compared with other assay results for antibody to viruses were as follows: cytomegalovirus, 98 and 100% (indirect hemagglutination assay); measles virus, 96 and 100% (enzyme-linked immunosorbent assay); and herpes simplex virus, 78 and 100% (indirect hemagglutination assay).

Rhesus monkey fetuses were inoculated with Venezuelan Equine Encephalitis (VEE) vaccine virus by the direct intracerebral route at approximately 100 days gestation to determine possible teratogenicity of the virus. Congenital micrencephaly, hydrocephalus and cataracts were found in all animals and porencephaly in 67 percent of the cases. The virus replicated in the brain and other organs of the fetus. VEE vaccine virus is teratogenic for non-human primates and must be considered a potential teratogen of man.

Five drug regimens for the treatment of acute toxoplasmosis were compared in a monkey model. Systemic disease that is almost always fatal in squirrel monkeys within 7-9 days was produced by oral inoculation of a brain suspension made from mice chronically infected with the Beverly strain of Toxoplasma gondii. All untreated controls died of toxoplasmosis (6/6) while treatment gave the following results: sulfamethoxazole, 0/3; spiramycin, 5/5; clindamycin/sulfadiazine (CLD/SLD), 0/4; pyrimethamine/sulfadiazine (PYR/SLD), 0/5; trimethoprim/sulfamethoxazole (TMP/SMZ), 0/4. Three of the five monkeys treated with CLD/SLD died during or shortly after the experiment from probable CLD toxicity. Sulfonamides alone or in combination with PYR or TMP were significantly more effective than spiramycin in treating toxoplasmosis in this model. The dose regimen used in this study did not allow us to determine if the addition of PYR or TMP changed the protection of sulfa alone.

A total of 301 female and 133 male Cebus monkeys have been placed under study during a 3-year period. Females are inoculated intradermally into the cervix every 6 months; 225 receive virus and 76 receive control material. More than 50% of the animals were infected on primary inoculation, and a similar percentage was foundon the 1st reinoculation. Males are housed with females at 1:1 to 1:3 ratios. Eighteen % of the males exposed to virus-inoculated females have become infected. To date, a total of 55 pregnancies have produced 14 live births and 8 abortions. The remaining 33 animals are still pregnant. No neonatal herpes simplex virus type 2 infections have been identified. Cytological changes of mild (atypia) to moderate (dysplasia) anaplasia have persisted for 12 to 32 months in 13 herpes simplex virus type 2-infected females. These animals received their 1st inoculation 14 to 50 months ago. Persistent anaplasia has not been found in control animals.

Rubella serology as performed by certain clinical laboratories is not always satisfactory. Until all the laboratory methods are improved, physicians should save all rubella sera for 1 year so that repeat testing may be conducted. The answer to the problem must come from improvements in rubella serologic tests being offered, plus improved laboratory performance and monitoring to ensure valid serologic data.

The clinical course and outcome of 58 pregnancies in 57 women with culture-verified genital herpes simplex virus (HSV) infection during gestation are reported. In 19 cases (33%) an active genital HSV infection was present within 1 week of delivery. Of the 60 infants delivered, 58 survived. No maternal or perinatal morbidity or mortality was attributable to HSV. This experience suggests that weekly culturing of the cervix and all other previously infected genital sites from the 36th week of gestation until delivery is an acceptable plan for managing such pregnancies. Women without evidence of infection at the onset of labor can be allowed to deliver vaginally. With appropriate precautions, breast-feeding by mothers with genital HSV infections is not contraindicated.

This study was designed to determine the incidence of previous and current herpesvirus hominis Type II infections in asymptomatic pregnant women. Sera were obtained from 985 patients for detection of Type I and II herpesvirus hominis antibodies. In addition 770 cervical and 211 amniotic fluid cultures for herpesvirus hominis Type II were performed. Identification of previous herpesvirus hominis infection was determined in 352 patients (35.7%) by calculation of a Type II/I antibody index of 85 or greater. Type II herpesvirus hominis was isolated from five cervical cultures for a 0.65% antepartum incidence of infection. None of the amniotic fluid cultures demonstrated virus. The significance of these findings is discussed.

Seventeen relatively young patients, ages 31-65 years (average, 45) with prior poliomyelitis, who after a number of years of stability had experienced new neuromuscular symptoms, were studied. Seven patients had deterioration of functional capacity and then stabilization without new muscular weakness. The other 10 had late postpoliomyelitis muscular atrophy (late PPMA ) characterized by focal progressive muscle weakness, wasting, fasciculations, and muscle pains affecting previously spared muscles or muscles previously affected but recovered. Four patients with late PPMA had lymphorrhages or lymphocytic infiltrates in their biopsied muscle; three of three patients had oligoclonal IgG bands in their spinal fluid, and five had variable peripheral T lymphocyte-subset ratios. In one patient with late PPMA , antibodies to poliovirus were specifically elevated in the cerebrospinal fluid. Our findings indicate that new motor-neuron disease can occur in patients with prior poliomyelitis and that immunopathologic mechanisms may play a role.

Numerous studies have suggested that opsonic antibody is important in neonatal immunity to group B streptococci. Immunoglobulin G is primarily transferred from the mother to the fetus across the placenta in the last few weeks of pregnancy. Premature babies may, therefore, not acquire sufficient opsonic antibody to protect them from infection with group B streptococci. Although maternal immunization may provide adequate maternal opsonic antibody, premature infants with antibody deficiency may remain susceptible to infection. Intravenous immunoglobulin administered to term pregnant rhesus monkeys did not provide reliable levels of serum opsonic activity to group B streptococci in their offspring. Pharmacokinetic and safety studies were also performed in human neonates. Significant elevations in group B streptococcal-specific IgG did occur in human neonates given 500 mg/kg intravenous immunoglobulin and the infusions appeared safe and well tolerated. The availability of intravenous immunoglobulin with functional activity against group B streptococci may provide a rapid and effective method of delivering opsonic antibody to neonates.

A sensitive enzyme-linked immunosorbent capture assay using biotin and streptavidin (capture B/SA ELISA) was developed using type-specific monoclonal antibodies for typing of herpes simplex virus. Rabbit anti-herpes simplex virus immunoglobulin G was used as the capturing antibody, and biotin-linked type-1-specific mouse monoclonal antibody or rabbit type-1- or type-2-specific polyclonal antibody served as the detecting antibody. The captured antigen was detected by an ELISA with alkaline phosphatase-conjugated streptavidin, which reacted with biotin molecules on the detector antibody. The capture B/SA ELISA was compared with other methods for efficiency and reliability in typing. Results obtained by restriction endonuclease digestion of the radiolabeled viral genome were used to determine the type (1 or 2) of clinical isolates. These results were then used as a reference for determining the accuracy of the capture B/SA ELISA, as well as that of the immunofluorescence method, both of which are easily adaptable for use in the clinical laboratory. The three methods were in perfect agreement. It was determined that both the capture B/SA ELISA and the immunofluorescence method using monoclonal antibodies provided typing results with 100% specificity and 100% sensitivity and thus were accurate and reliable. However, the ELISA was the method of choice because of its simplicity, rapidity, and use of nonradioisotopic reagents.

Several groups have reported a relation between herpesvirus hominis infection and certain psychiatric disorders. We have investigated herpes antibody levels in chronic criminal offenders who were diagnosed as defective delinquents and in criminals who were not defective delinquents. We found no difference in the frequency of titers of herpesvirus type I or type 2 antibody in these groups.

The latex agglutination card test (Rubascan) for the detection of rubella antibody was compared with the standard hemagglutination inhibition and enzyme-linked immunosorbent assay tests. There was complete agreement with sera which had hemagglutination inhibition titers of >/=16. Sera with low levels of antibody which were positive in the enzyme-linked immunosorbent assay, however, gave negative latex agglutination results approximately 25% of the time (false negatives), whereas sera which were negative in the enzyme-linked immunosorbent assay gave false-positive results in about 3% of the cases. The use of capillary "finger stick" plasma instead of venous sera resulted in additional false-negative latex agglutination tests among patients with very low antibody titers. Because of the simplicity of the method, it should be possible to use this test in physicians' offices and in large immunization campaigns. Care should be taken to become completely familiar with the procedures and reading of the agglutination patterns. Control sera should always be used. Interpretation of results should take into consideration the rates of false-negative and false-positive results noted above. These rates apply to sera with little or no antibody. In particular, negative tests should be confirmed with more specific methods in critical cases, such as pregnant women exposed to rubella or women of childbearing age who are being considered for immunization. There was no problem with the latex agglutination findings for sera with higher titers. Since results are available in 8 min, physicians should be able to counsel their patients rapidly and immunize, if necessary, while the patient is still present.

Gestational herpesvirus infections can significantly alter the outcome of pregnancy. Potential hazards to the embryo, fetus, or neonate are numerous and depend on several variables, including the specific virus involved, gestational timing of infection, and whether the infection is primary or recurrent in nature. This article reviews the epidemiology and clinical manifestations of maternal, fetal, and neonatal herpesvirus infections, methods for establishing an accurate etiologic diagnosis, and prevention strategies, including prospects for prenatal diagnosis of these infections.

Herpes simplex viruses cause common mucocutaneous infections, but many aspects of their epidemiology and transmission are incompletely defined. Although the incidence of oral herpes remains relatively unchanged, the incidence of genital herpes is increasing significantly. Definitive diagnosis of herpes remains dependent on virus isolation, but techniques involving direct examination of clinical specimens are increasingly sensitive and may simplify and speed diagnosis. With the advent of acyclovir, effective therapy and suppression of infection are feasible for immunodeficient and selected normal patients. Unanswered questions remain regarding the long-term safety of acyclovir and the potential for emergence of clinically significant drug resistance. No effective vaccines are yet available for herpes virus infections. Promising strategies for vaccine development include preparation of immunogenic proteins, engineering of specially attenuated live virus strains, and incorporation of selected herpes genes into live vaccinia virus vectors.

Inhalation of undiluted, aerosolized measles vaccine was immunogenic in 100% of 4- to 6-month-old and older children with and without residual maternal antibody when the human diploid cell (HDC) vaccine containing the Ikić (Edmonston-Zagreb) strain and 1% human albumin was used but in a smaller percentage of infants given a chick embryo fibroblast (CEF) vaccine, which contained the Edmonston-Schwarz strain, ten times more virus, and hypertonic sugar solution but no added protein. Prevaccination residual placentally transmitted plaque-neutralizing antibody titers of 25 to 512 that can prevent an immune response after subcutaneous injection of measles vaccine did not prevent an immune response after inhalation of aerosolized vaccine. There were no immediate clinical reactions in the 160 children who inhaled the aerosolized vaccines, and no significant subsequent reactions among the 96 children who were successfully immunized. There were no contact infections.

We report a seven-year follow-up of identical twins, in one of whom subacute sclerosing panencephalitis (SSPE) developed. Primary measles infection occurred simultaneous in both twins at age 4. The affected twin sustained a grade 1 closed head injury within six months of her primary measles infection. At age 13, SSPE was diagnosed following the onset of personality change and myoclonic seizures. Measles antibody level was elevated in the serum and CSF. After remaining in stage 2 for five years, rapid mental and neurological deterioration occurred. Measles antibody level remained elevated, and oligoclonal IgG was present in both serum and CSF. Results of neurological examination as well as virological and immunological tests were normal in the unaffected twin. Besides the occurrence of head injury, factors known to be associated with SSPE were not obviously different in the twins. We have been unable to determine a difference that would easily explain the occurrence of SSPE in only one of two identical twins.

Sera from patients and employees of the Lynchburg Training School and Hospital were tested for Hepatitis B surface antigen by complement fixation test and antibody against Hepatitis B surface antigen by radioimmunoprecipitation test. Hepatitis B surface antigen was detected in 20% of the Down's syndrome patients and 7 percent of the matched other retarded patients. Antibody against Hepatitis B surface antigen was detected in 40% of the Down's syndrome and 57% of the matched other retarded patients. Hepatitis B virus infection as measured by presence of either Hepatitis B surface antigen or antibody was similar in the Down's syndrome patients (59%) and the matched other retarded patients (63%). Male patients had a higher frequency of Hepatitis B surface antigen chronic carriers and a lower frequency of antibodies to Hepatitis B surface antigen than the female patients. No relationship between age at time of first institutionalization and prevalence of Hepatitis B virus infection was demonstrated. However, it was observed that patients institutionalized at an earlier age were more likely to be housed in wards with a high frequency of Hepatitis B surface antigen. Increased length of institutionalization was associated with increased prevalence of Hepatitis B virus infection. Antibody to Hepatitis B surface antigen was detected in 33% of the employees. Employees who worked on wards with a high frequency of Hepatitis B virus infection had a high frequency of Hepatitis B surface antibody (50%) whereas those working on wards with a low frequency of infection had a low frequency of Hepatitis B surface antibody (9%).

The occurrence of hepatitis A early in pregnancy has been reported to result in increased births of children with Down's syndrome. Eleven sets of paired sera were obtained before conception and during pregnancy from women who delivered infants with Down's syndrome. These sera were tested for antibody to hepatitis A virus with use of immune electron microscopy. None of the women had seroconversions or increases in levels of antibody to hepatitis A virus. No evidence of an association between hepatitis A and Down's syndrome was found in the women studied.

Using the technique of in situ DNA-to-DNA hybridization, a JC virus biotinylated DNA probe was developed and applied to formalin-fixed, paraffin-embedded, or fixed, frozen sections of brain tissue from three subjects with progressive multifocal leukoencephalopathy (PML). Light microscopy was carried out to correlate the presence of JC virus DNA with the selective infection of oligodendrocytes and astrocytes in PML. Oligodendrocytes (lytically infected) showed the greatest evidence of viral DNA. More astrocytes showing bizarre morphological changes had evidence of viral DNA than did astrocytes that were simply reactive. Viral DNA was not evident in vascular endothelial cells using this technique. Viral DNA replication may be an important initial step which produces the bizarre "transformed" astrocytes of PML. Findings in this study do not support the hypothesis that vascular endothelial replication is important in the pathogenesis of JC virus-induced PML. In situ hybridization with biotinylated JC virus probe may be useful in the diagnosis of PML on brain biopsy specimens.

Group B streptococci (GBS) are responsible for serious infections of newborn infants. An experimental model for GBS infection was developed in the newborn rhesus monkey in order to obtain more information concerning the pathogenesis of such infections. A series of 29 newborn monkeys were inoculated with either type Ic or type III GBS or sterile broth. Fatal neonatal meningitis without associated pneumonia was produced consistently following intracerebral inoculation with either type Ic or type III; intracerebral inoculation with sterile broth produced no apparent disease. Variable disease production followed intravenous or intra-amniotic GBS inoculation, and clinical manifestations ranged from no apparent disease to fatal meningitis and pneumonia. This monkey model may be useful for further investigation of treatment and prevention of neonatal GBS infection.

Paired sera from 21 women whose children had malignancy and 15 women who were diagnosed as having abnormal pathology in the cervix and matched normal controls were studied for presence of BK antibodies by the ELISA technique. BK antibody was detected in 74% of the women in the first serum sample obtained. Evidence of BK antibody rises were observed in eight of 72 women (11%) and was distributed equally among women with abnormal children and women with abnormal pathology in the cervix and controls and that the level of antibody was not influenced by vaccination with killed polio vaccine during this pregnancy. Our serological data fails to show an association between infection with BK virus and malignancy in the children or carcinoma in situ of the cervix.

The longitudinal study of approximately 60,000 pregnant women was conducted at 14 major medical centers throughout the United States. Clinical data was obtained under prescribed protocols for each of the study women throughout their pregnancy, at delivery, and through the postpartum period. The children were followed with uniform examinations from birth through seven years of age. In addition blood samples were taken from the pregnant women at registration, every two months through pregnancy, at delivery, and six weeks postpartum. Cord blood samples were also taken from the children during the last half of the study. We have used this material from the Collaborative Perinatal Project for the investigation of the role of infections in the production of damage to the fetus and newborn. The frequency of clinically recognizing infection during pregnancy was determined and geographic variation was demonstrated. Serological tests were used to document certain diseases. The frequency of confirmed clinical cases per 10,000 were: rubella, 8; rubeola, 0.6; mumps, 10; varicella-zoster, 5. The epidemiology and clinical findings associated with infections were studied using serological methods. This has provided data on the frequencies of infections such as cytomegalovirus, herpes simplex, mumps, rubeola, respiratory syncytial virus, and others. The study of abnormal pregnancies and matched controls is in progress using serological techniques. A number of specific studies have been reported on infections including rubella, neonatal meningitis, cytomegalovirus, maternal urinary tract infections, and toxoplasmosis. Further testing is now in progress employing more sophisticated laboratory methods and more complete data analysis.

TORCH tests can be used to document immunity or recent infections. Many laboratories now offer TORCH tests and there are a large variety of methods, kits, and reporting systems. Some of the TORCH tests are not accurate and should be avoided. In general, we prefer enzyme immunoassays for documentation of past infections or immunity. To demonstrate recent infections with toxoplasmosis and rubella we use IgM enzyme-linked immunosorbent assay tests but for cytomegalovirus and herpes infections we prefer virus isolation. Physicians should send specimens only to laboratories that participate in proficiency surveys or similar tests that document the accuracy of the laboratory. All TORCH test sera should be held by the laboratory for 1 year to permit repeat testing and analysis with subsequent specimens if necessary.

There are a large number of infectious agents which damage or kill the developing fetus or child. In this report I have summarized the changing status of information available for just six of these diseases. For rubella there has been excellent success with the development of a vaccine for prevention of this disease. Unfortunately the vaccine is only used extensively in a few countries. Herpes simplex has become a particular problem because of the rapid increase in the frequency of genital herpes infections, the spontaneous recurrences of the lesions, and the difficulty in prevention or treating congenital infections. Cytomegalovirus infections are now known to occur in 1% of newborns, and some damage is produced in about 10% of these children. We have no methods for preventing or treating this infection. Varicella at term is also an important risk to the child but this can now be controlled by the use of VZIG. Varicella earlier in pregnancy may be teratogenic. Venezuelan equine encephalitis virus can cause severe brain damage to the fetus, and one of the vaccines for this infection was shown to be teratogenic in monkeys. Lastly, congenital toxoplasmosis has been known for many years to cause fetal damage and death. Further studies of serological detection of infection and treatment are needed. A number of other viral, bacterial, and parasitic diseases must also be considered as part of the total group of these preventable causes of physical and mental damage to the fetus and newborn.

The major goal of rubella immunization is the prevention of the congenital rubella syndrome. As many as 20 per cent of women in the reproductive age group in the United States continue to be susceptible to rubella despite the immunization programs currently in place. Intensified efforts are therefore needed to identify persons at risk for infection and to vaccinate them. Women who develop a rubella-like illness during pregnancy should have the diagnosis confirmed serologically because a diagnosis based on clinical criteria alone is unreliable and because of the serious implications of gestational rubella infection. The rubella virus can infect the fetus at any stage of pregnancy, but defects are rarely noted when this occurs after the 16th week of gestation. The most common abnormalities in the congenital rubella syndrome are hearing loss, mental retardation, cardiac malformations, and eye defects. Diabetes mellitus, thyroid disease, glaucoma, and other delayed manifestations of congenital rubella syndrome are common, thereby necessitating long-term followup of these patients. The detection of rubella-specific IgM antibodies in fetal blood is helpful in establishing the diagnosis prenatally and can aid in the management of pregnancies complicated by this infection. Susceptible women identified through screening during pregnancy should be immunized in the immediate postpartum or postabortion period. Although the live, attenuated rubella vaccine is contraindicated during pregnancy, pregnant women who are inadvertently immunized are not candidates for pregnancy termination because no defects consistent with congenital rubella have been reported to date in the offspring of other similarly vaccinated women.

A tumor cell suspension of an explanted JC virus (JCV)-induced owl monkey glioblastoma was inoculated intracranially into four recipient juvenile owl monkeys. Twenty-eight months following inoculation one owl monkey developed a glioblastoma, which was explanted into tissue culture. DNA from both the tumor tissue and tumor cells in culture hybridized to a JCV DNA probe by Southern analysis, indicating that free, as well as integrated, viral DNA may be present. At the time of the second culture passage, viral JCV DNA was extracted from these cells and cloned into a plasmid vector. Nucleotide sequencing of the regulatory region of the cloned DNA demonstrated homology with the prototype Mad-1 strain of JCV and revealed a 19-base-pair deletion in the second 98-base-pair tandem repeat that eliminated a second TATA box. This deletion is characteristic of the Mad-4 strain of JCV, which is highly neurooncogenic. By the third culture passage, 100% of the cells were T-antigen positive. Approximately one-third of the cells in culture hybridized to a biotinylated JCV DNA probe when in situ hybridization was used, a technique that only detects high-copy-number of replicating viral sequences. By the culture passage 5 and continuing through culture passage 14, viable JC virions could be recovered. The T protein synthesized by this virus, now termed JCV-586, differed from both the Mad-1 and Mad-4 strains in that it formed a stable complex with the cellular p53 protein in the tumor cells. Also, the JCV-586 T protein reacted to several monoclonal antibodies made to the simian virus 40 T protein that were not recognized by either the Mad-1 or Mad-4 strains.