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Biomedical subjects

J L Melnick

Publications and source records attributed to J L Melnick.

At least 37 records · Page 2Linked to original sources

Age differences in immunity against wild and vaccine strains of poliovirus prior to the 1988 outbreak in Israel and response to booster immunization.

During the 1988 type 1 polio outbreak in Israel, most cases occurred in previously vaccinated subjects aged 11-30 years, suggesting a possible age-related immunity deficit against the wild virus responsible for the outbreak. We examined type 1 poliovirus neutralizing antibody titres against the Sabin strain, the standard wild strain (Mahoney), the wild strain responsible for the 1988 outbreak and a previous wild strain from the region, on frozen sera drawn prior to the mass vaccination campaign from subjects aged 6 to 40 years. Response to vaccination with oral poliovaccine (OPV) was examined in a subgroup aged 18-40 years. At all ages, the highest antibody titres prior to the outbreak were against the Sabin strain. Geometric mean titres (GMTs) against both the Sabin strain and the wild Mahoney strain were significantly higher in the age groups 6-7, 12-13 and 30-40 years compared with the 18-29-year-olds. For the other wild strains, the GMT for those aged 30-40 years was significantly and substantially higher than in the other age groups, followed by the 12-13- and 6-7-year-olds and lowest in those aged 18-29 years. Following vaccination with OPV in subgroups aged 18-29 and 30-40 years, GMTs against Sabin and all wild strains were similar to each other and in both age groups. These findings suggest that there was a relative immunity gap against the wild type 1 strains in the age group that lacked prior exposure to wild virus and had received the last OPV dose more than 17 years previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Albert B. Sabin.

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History, 20th Century↗

Cytomegalovirus and atherosclerosis.

An avian herpesvirus is known to cause atherosclerosis in chickens. The same virus can induce a proliferative disease, malignant lymphoma, suggesting that this agent may also have transforming potential and thus stimulate the proliferation of arterial smooth muscle cells, a prominent feature of atherogenesis. The evidence for involvement of cytomegalovirus (CMV), a member of the human herpesvirus family, in atherosclerosis is much more circumstantial. The finding of CMV antigen and nucleic acid sequences in arterial smooth muscle cells of humans suggests that viral infection of the arterial wall may be common in the general population, including patients with severe atherosclerosis. In seroepidemiological studies, high levels of CMV antibodies were found to be associated with clinically manifest atherosclerotic disease, suggesting that a periodically activated latent infection or a continuously active infection is present in patients with atherosclerosis. Since the viral genome but not infectious virus is found in arterial cells, the artery itself may be the site of CMV latency. Of particular significance is the recent finding that heart transplant recipients, who are immunosuppressed, and who are also actively infected with CMV, are prone to develop accelerated atherosclerosis in the transplanted organ. Although suggestive, these observations by themselves do not demonstrate that viruses have a role in the pathogenesis of atherosclerosis, but they support a working hypothesis of the steps involved.

Animals↗

Properties and classification of hepatitis A virus.

Hepatitis A virus (HAV) is a member of the picornavirus family. It was first provisionally classified as enterovirus 72, but subsequent determinations of its nucleotide and amino acid sequences showed them to be sufficiently distinct to assign the virus to a new genus. Heparna-virus (Hep-A-RNA-virus) has been suggested as the genus name. HAV shares the key properties of the picornavirus family: an icosahedral particle 28 nm in diameter with cubic symmetry, composed of 30% RNA and 70% protein. The genome is single-stranded 7.48 kb RNA, linear and positive-sense. Like other picornaviruses, HAV possesses four major polypeptides cleaved from a large precursor polyprotein. The surface proteins VP1 and VP3 are major antibody-binding sites. The internal protein VP4 is much smaller than the VP4s of other picornaviruses. As other picornaviruses, HAV has no envelope and replicates in the cytoplasm. HAV is stable to treatment with either and acid, and is much more heat-resistant than other picornaviruses. It withstands 60 degrees C for 1 h. MgCl2 stabilizes the virus to withstand temperatures up to 80 degrees C. The relative resistance of HAV to disinfection indicates a need for extra precautions in dealing with hepatitis patients and their products. Only one serotype is known. There is no antigenic cross-reactivity with other hepatitis viruses. HAV initially was identified in stool and liver preparations by employing immune electron microscopy as the detection system. Chimpanzees and marmoset monkeys are susceptible to HAV. HAV has been cultivated serially in primary explant cultures of adult marmoset livers and in cell lines of primate origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Virus inactivation: lessons from the past.

The organizers of this meeting have assigned two tasks to me. The first is to describe the state of affairs in 1955 when several lots of Salk poliovaccine, which had been formalin-inactivated according to government regulation and had been released for use in children, were subsequently found to have retained a small amount of live virulent virus. The second task is to describe a series of experiments that we conducted 25 to 35 years ago on the influence of cations on the thermostability of viruses. Perhaps there are some lessons to be learned and some benefits for future research to be gained from this history.

Cations↗

Response to trivalent oral poliovirus vaccine with and without immune serum globulin in young adults in Israel in 1988.

Fifteen cases of type 1 paralytic poliomyelitis occurred in August 1988, mainly among young adults in the Jewish population of Israel, where vaccine coverage exceeds 90%. The military forces, as a precaution against further spread of the virus, vaccinated all recruits in late September. They received oral poliovirus vaccine (OPV) simultaneously with prophylactic immune serum globulin (ISG) to protect against hepatitis A virus infection. Since it is generally not recommended to administer live vaccines simultaneously with ISG, the serologic response to OPV given at the same time as ISG was compared with the response when OPV was given alone; specimens were also available from a control group receiving ISG alone. No effect of ISG on the antibody response to OPV was found, and thus there appears to be no contraindication to giving OPV at the same time as injecting pooled ISG--particularly relevant for travelers to areas endemic for both diseases, who have to leave at short notice. Of recruits 18-19 years of age, 21% lacked antibodies to type 1 poliovirus, suggesting either a decline in antibody titers with age or a lack of vaccine potency during earlier years. After the booster, only 2% lacked type 1 antibody, and the geometric mean titer increased from 1:16 to 1:698.

Adult↗

Microculture assay for isolation of human immunodeficiency virus type 1 and for titration of infected peripheral blood mononuclear cells.

To define the optimal conditions for human immunodeficiency virus (HIV) detection in microcultures, experiments were conducted with different ratios of patient and donor peripheral blood mononuclear cells (PBMCs). Donor/patient PBMC ratios ranged from 1:1 to 1:125. Optimal results were obtained when 1,500,000 donor cells were cocultured with equal or smaller quantities of patient PBMCs. Thus, virologic endpoints could be achieved by diluting patient cells. Smaller numbers of donor cells, with or without larger numbers of patients cells, resulted in lower rates of HIV isolation. Similarly, the direct stimulation of patient PBMCs with phytohemagglutinin without the addition of normal donor cells lowered the sensitivity of the assay significantly. We suggest that a microculture procedure using a fixed quantity of donor cells with different dilutions of patient cells may be useful for monitoring changing HIV levels during antiviral therapy.

Cells, Cultured↗

Specific interaction of CD4-bearing liposomes with HIV-infected cells.

The CD4 molecule was reconstituted into the bilayers of large liposomes. Fluorescence microscopy and electron microscopy showed that these liposomes interact with HIV-infected H9-HT cells, delivering their contents to the cell interior. Liposomes bearing CD4 did not interact in this way with noninfected H9-HT cells nor did liposomes without CD4 interact significantly with HIV-infected cells. From electron micrographs, it appeared that HIV binds to liposomes bearing CD4; no attachment of virions to liposomes without CD4 was observed.

CD4 Antigens↗

AIDS in Bulgaria.

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Acquired Immunodeficiency Syndrome↗

Smoking and infectious agents and risk of in situ cervical cancer in Sydney, Australia.

In a study of 116 in situ cervical cancer patients and 193 matched community controls in Sydney, Australia, smoking was found to be a major risk factor. Current smokers had a adjusted relative risk [RR] of 4.5 compared to nonsmokers [95% confidence interval (CI) 2.2-9.1] and exsmokers a RR of 1.3 [95% CI 0.6-3.0]. There was a stepwise dose-response relationship between risk and number of cigarettes smoked (30+ cigarettes/day, RR = 5.1, 95% CI 1.5-17.3); this dose-response relationship was more marked among current smokers. Years of cigarette smoking was not consistently related to risk. Exposures to herpes simplex virus type 2 and cytomegalovirus as measured by antibody prevalence were unrelated to risk (RR = 1.1 for both measures). However, cases appeared to have more exposure than controls to herpes simplex virus type 1 (RR = 2.3, 95% CI 1.1-4.4).

Adolescent↗

Viral vaccines: achievements and challenges.

In this review the present state of vaccination as a means to control viral diseases is discussed, and the needs and directions for future investigations are considered. The history of viral vaccines already in use is surveyed for guidance in what steps and background knowledge of the viral agents and the host responses to infection were necessary to their successful development. The steps requisite for demonstrating efficacy and safety of a viral vaccine also are summarized, and the features of the target populations to be protected are noted as they affect the final requirement for a successful vaccine: that it be administered in proper dosage and potency to those who need it. General remarks on the proper use of current vaccines are followed by an overview of various developments toward prospective vaccines, along with the predicted time-frames for their coming into general use. Vaccines considered include vaccines to be administered locally at the portal of entry, subunit vaccines, viruses attenuated by genetic manipulation, use of viral vectors, vaccines developed by means of recombinant DNA, synthetic peptides, and anti-idiotype vaccines, as well as new vaccines being developed by more conventional methods.

Humans↗

Virus vaccines: principles and prospects.

The present status of vaccination for controlling viral diseases is reviewed, and the needs and directions for future investigations are discussed. A survey of viral vaccines now in use has shown that knowledge about the viral agents and about the hosts' responses to infection was essential for their development. The steps needed to demonstrate the efficacy and safety of a viral vaccine are summarized; the final requirement for a successful vaccine is that it be administered in proper dosage and potency to the target populations. After general remarks on the proper use of current vaccines there follows an overview of various developments in creating new vaccines, along with the predicted time-frames for their coming into general use. Topics considered include vaccines to be administered locally at the portal of entry, subunit vaccines, viruses attenuated by genetic manipulation, use of viral vectors, vaccines developed by means of recombinant DNA, synthetic peptides, and anti-idiotype vaccines, as well as new vaccines being developed by more conventional methods.

Humans↗