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Biomedical subjects

S Plotkin

Publications and source records attributed to S Plotkin.

At least 37 records · Page 2Linked to original sources
PubMed1996

Case presentation of calcaneonavicular coalition in monozygotic twins.

A case study of monozygotic twins with bilateral calcaneonavicular coalitions is presented. With the frequency of tarsal coalitions being approximately 1% to 2% and the frequency of monozygotic twins being 0.4%, it is a rare but predictable finding to see monozygotic twins with tarsal coalitions. This sheds additional light on the etiology of tarsal coalition that historically has been believed to be a defect in mesenchymal differentiation with indications of a genetic component. Despite the limited number of subjects used for various studies, tarsal coalitions have been considered to be an autosomal dominant defect with variable penetrance. In fact, inheritance of tarsal coalitions is more complicated than simple mendelian inheritance patterns and is likely to be a single error in a polygenic system. Because of this inheritance pattern, it is important to consider evaluating siblings and close family members of patients diagnosed with a tarsal coalition.

Adolescent↗
PubMed1992

Immunisation with canarypox virus expressing rabies glycoprotein.

Poxviruses have many useful features as vectors for genes that carry immunising antigens from other viruses, such as ease of production and induction of cellular and humoral immunity, but there is concern about the safety of vaccinia virus. We turned to an avian poxvirus (canarypox); this virus undergoes abortive replication in mammalian cells that enables presentation of early gene products to the immune system. Canarypox virus was used as a vector for the rabies glycoprotein G gene. The safety and efficacy of the recombinant (ALVAC-RG; vCP65) were tested in several animal species, then it was subjected to a phase 1 clinical trial. Twenty-five volunteers were randomly assigned to subcutaneous injections of the recombinant (three groups [A, B, and C] received two doses each of 10(3.5), 10(4.5), and 10(5.5) tissue-culture infectious doses50, respectively) or of human diploid cell culture vaccine (HDC; 6.52 international potency units per dose). 28 days after the second dose, all nine ALVAC-RG group-C subjects and two of three group-B subjects had rabies neutralising antibody concentrations of at least 0.5 IU/ml, the level associated with protection in animals. Although the geometric mean titre of these antibodies at that time was lower in group C than in the ten HDC recipients (4.4 [range 0.9-12.5] vs 11.5 [4.7-25.3] IU/ml), a single booster dose at 6 months induced a recall response in volunteers primed with either vaccine. Side-effects associated with ALVAC-RG were mild and of short duration and occurred at similar frequency to those of HDC vaccine. This study has shown the potential of non-replicating poxviruses as vectors for vaccination in human beings. Trials of canarypox-virus recombinants at higher doses and by other routes of administration are needed.

Adult↗
PubMed1992

Efficacy and safety of a Haemophilus influenzae type b capsular polysaccharide-tetanus protein conjugate vaccine.

A polyribosylribitol phosphate (polysaccharide)-tetanus protein conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) was evaluated for safety and efficacy after vaccination of more than 100,000 infants. No major side effects were attributed to the vaccine. Immunogenicity studies showed an antibody response in 70% to 100% of infants after two doses, and in 98% to 100% of infants after three doses, within the first 6 months of life. Antibodies persisted in 90% of recipients, in whom significant anamnestic responses developed after a booster dose at 18 months of age. In comparison with other available Hib vaccines, PRP-T induces equal or higher mean titers after three doses. Although licensure of other vaccines interrupted controlled efficacy trials, up to that point five cases of Hib disease in those trials had occurred in placebo recipients, and no Hib disease has been reported in the more than 100,000 vaccinated infants who have received more than one dose of PRP-T. Thus PRP-T combined immunogenicity early in life with induction of immunologic memory.

Bacterial Vaccines↗
PubMed1992

Safety and immunogenicity of acellular pertussis vaccine combined with diphtheria and tetanus toxoids in 17- to 24-month-old children.

A double-blind, randomized, controlled trial comparing 4 lots of acellular pertussis-diphtheria tetanus toxoids vaccine (APDT) to whole cell DTP vaccine in 397 children was conducted at 7 clinical centers. Children were immunized at 17 to 24 months of age and sera were obtained pre- and postimmunization. Sera were analyzed for antibody to pertussis antigens (pertussis toxin, filamentous hemagglutinin, with a molecular weight of 69,000 (69k) outer membrane protein and agglutinogens) and to diphtheria and tetanus toxoids. Information concerning local reactions and systemic events was collected daily for 10 days postimmunization. The acellular vaccine produced significantly fewer local reactions than whole cell DTP. Parents reported that drowsiness or fretfulness occurred significantly less often in APDT vaccine recipients compared with whole cell DTP recipients. Fever greater than or equal to 38.3 degrees C occurred in 8% of APDT vaccine recipients and in 15% of whole cell DTP vaccine recipients (P = 0.06). The only significant difference in immune response to pertussis antigens between the two vaccines was for filamentous hemagglutinin (P less than 0.01) for which significantly higher antibody concentrations were found in the APDT vaccine group. We conclude that this APDT vaccine is safe and immunogenic when administered as a booster dose to 18-month-old children.

Antibodies, Bacterial↗
PubMed1992

Generation of deletion mutants of simian immunodeficiency virus incapable of proviral integration.

Deletion mutants of simian immunodeficiency virus (SIVmac) which were unable to integrate into host cells were generated by removing a portion of the integrase (IN) domain of the pol gene. The resulting plasmid was transfected into HUT-78 and human rhabdomyosarcoma cells. In comparison with the parental plasmid DNA transfected in parallel, the deletion mutant was found to direct efficient production of virus in both cell systems. Viruses derived from wild-type and mutant proviral DNAs were also tested for their relative replicative abilities in HUT-78 and U937 cells, and the kinetics of virus production was found to vary between these two cell systems. Analysis of DNA from infected cell nuclei showed that the deletion mutant lacked the ability to integrate despite being able to produce infectious virus. Using the sensitive polymerase chain reaction technique, we have clearly demonstrated the absence of the IN domain in the deletion mutant after infection and replication in HUT-78 cells. Such mutants might form the basis for the development of an experimental live attenuated vaccine.

Base Sequence↗
PubMed1991

A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection. METHODS: Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease). RESULTS: After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects. CONCLUSIONS: In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.

Acyclovir↗
PubMed1991

Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: In a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus (HSV) infection, we found no significant difference between the treatments in adjusted mortality and morbidity. Hence, we sought to define for the entire cohort (n = 202) the clinical characteristics that best predicted the eventual outcome in these neonates. METHODS: Data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed HSV infection. We examined the outcomes by multivariate analyses of 24 variables. Disease was classified in one of three categories based on the extent of the involvement at entry into the trial: infection confined to skin, eyes, or mouth; encephalitis; or disseminated infection. RESULTS AND CONCLUSIONS: There were no deaths among the 85 infants with localized HSV infection. The mortality rate was significantly higher in the 46 neonates with disseminated infection (57 percent) than in the 71 with encephalitis (15 percent). In addition, the risk of death was increased in neonates who were in or near coma at entry (relative risk, 5.2), had disseminated intravascular coagulopathy (relative risk, 3.8), or were premature (relative risk, 3.7). In babies with disseminated disease, HSV pneumonitis was also associated with greater mortality (relative risk, 3.6). In the survivors, morbidity was most frequent in infants with encephalitis (relative risk, 4.4), disseminated infection (relative risk, 2.1), seizures (relative risk, 3.0), or infection with HSV type 2 (relative risk, 4.9). With HSV infection limited to the skin, eyes, or mouth, the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences.

Consciousness↗
PubMed1991

Distribution of bacteria in the operating room environment and its relation to ventricular shunt infections: a prospective study.

In order to study the distribution of bacteria in the operating room environment, cultures were obtained during 111 unselected shunt operations throughout a 10-month period. After routine skin preparation, bacteria were collected by placing Millipore filters on the patient's prepped skin underneath the drapes, on top of the drapes in the operative field, and/or on the sterile instrument table, and left in place for the duration of the case. In 48 patients, full-thickness skin biopsies taken at the initial incision were cultured in lieu of skin surface cultures. Perioperative cerebrospinal fluid cultures and subsequent shunt infections were monitored. Of the 288 environmental (skin and surfaces) cultures, 24 were positive (20 coagulase-negative Staphylococcus and 4 Staphylococcus aureus). Positive cultures were found in 15 of 111 drape cultures (13.5%), 7 of 77 instrument table cultures (9.1%), and 2 of 97 skin cultures (2.1%). Positive environmental cultures were not correlated with the surgeon, length of case, time of day, or type of shunt operation, but were more likely to occur in a room other than the designated neurosurgical operating room. There was a correlation between the occurrence of positive environmental cultures and positive cerebrospinal fluid cultures, although the organisms were not always the same. Coagulase-negative Staphylococcus was the most common organism isolated from all sites. We conclude that bacteria most often associated with shunt infections are airborne in the operating room, rather than originating from the patient's skin, and are distributed in the highest concentration near the surgical team.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

High expression of human cytomegalovirus (HCMV)-gB protein in cells infected with a vaccinia-gB recombinant: the importance of the gB protein in HCMV immunity.

The human cytomegalovirus (HCMV), Towne strain, glycoprotein B (gB) gene was cloned into a vaccinia vector (Copenhagen strain) under the control of the H6 early and late vaccinia promoters (Vac-gB recombinant). The gB protein was expressed in a high percentage of the Vac-gB-infected cells throughout the virus replication cycle. Cytosine-arabinoside (ara-C) did not influence the expression of the gB protein early after infection (5 h), but did inhibit it later in viral replication (7-29 h). The Vac-gB recombinant induced HCMV neutralizing antibodies in guinea-pigs. Cells infected with the Vac-gB recombinant absorbed 50-88% of neutralizing activity of human sera obtained from volunteers previously inoculated with the Towne or Toledo strains and from naturally seropositive individuals.

Animals↗
PubMed1990

Characterization of multiple molecular interactions between human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 (HIV-1).

In transient gene expression assays we observed an increase in expression of the bacterial chloramphenicol acetyl-transferase (CAT) gene, under the transcriptional control of the HIV-1 LTR (pLTR-CAT), when this plasmid was cotransfected into Vero or MRC-5 cells with a plasmid containing either the HCMV immediate early 1 and 2 (E1, IE2) genes (pRL43a) or just the IE2 gene (pMP18). When the HCMV IE1 gene (pMP12) was cotransfected with pLTR-CAT into Vero cells the level of measurable CAT gene activity was below the level observed when pLTR-CAT was cotransfected with a nonspecific carrier plasmid (pGEM3). The negative influence of the HCMV IE1 gene product on the HIV-1 LTR in Vero cells was also observed when the HIV-1 tat gene (pLTR-TAT) was contransfected into Vero cells with pLTR-CAT and pMP12. However, when the HCMV IE1 gene was cotransfected into rhabdomyosarcoma (RD) cells with proviral HIV-1 DNA, an increase in viral production, as monitored by measurement of HIV-1 reverse transcriptase activity, was observed. In electrophoretic mobility shift assays, nuclear extracts obtained 15 hr post-HCMV infection (hpi) were found to contain a lower level of interaction with an oligonucleotide which corresponded to the HIV-1 LTR Sp-1 binding motif. Nuclear extracts obtained 40 hpi of MRC-5 cells had a greater level of interaction with, and changed the mobility of, the Sp-1 oligonucleotide relative to the uninfected nuclear extracts. HCMV-infected MRC-5 cell nuclear extracts also contain a factor(s) which interacted with the HIV-1 LTR between nucleotide positions -15 to -2 relative to the HIV-1 mRNA start site.

Animals↗
PubMed1990

Isolated gA/gB glycoprotein complex of human cytomegalovirus envelope induces humoral and cellular immune-responses in human volunteers.

Three human cytomegalovirus (HCMV) seronegative individuals were immunized with a single dose of HCMV envelope; two individuals developed neutralizing antibodies. Two naturally HCMV seropositive and three HCMV seronegative human volunteers were immunized with a major glycoprotein complex, gA/gB, of HCMV that had been purified by immunoadsorbent column chromatography. After a single injection of the gA/gB preparation, the naturally seropositive individuals developed higher titres of neutralizing antibodies and temporarily higher HCMV-specific lymphocyte proliferation (HCMV-LP) responses in vitro. The seronegative individuals developed neutralizing antibodies after the third injection of gA/gB, which were present only transiently, but showed a rapid reappearance and increase in titre after the fourth injection. At 1 year after the first injection, the neutralizing antibody titres were still comparable with those of the naturally seropositive individuals. HCMV-LP responses to HCMV in the initially seronegative individuals developed after the second or third injection with the gA/gB preparation and remained positive during the 1-year observation period. These results show that the gA/gB protein induces both humoral and cellular immune responses in humans, and might serve as the basis of a subunit vaccine.

Animals↗
PubMed1989

Human cytomegalovirus induces stage-specific embryonic antigen 1 in differentiating human teratocarcinoma cells and fibroblasts.

Cell surface expression of stage specific embryonic antigen 1 (SSEA-1), or Lex (III3 FucnLC4), was induced in differentiated human teratocarcinoma cells and in human diploid fibroblasts 3-6 d after infection with human cytomegalovirus (HCMV). In parallel, fucosylated lactoseries glycolipids bearing the SSEA-1/Lex epitope were readily detected in the infected cells but not in the uninfected cells. HCMV infection also results in altered expression of several glycosyltransferases. SSEA-1/Lex induction is probably a consequence of both increased expression of beta 1----3N-acetylglucosaminyltransferase, which catalyzes the rate-limiting step in lactoseries core chain synthesis, and subtle alterations in the relative competition for common precursor structures at key points in the biosynthetic pathway. Since SSEA-1 has been suggested to play a role in some morphogenetic cell-cell interactions during embryonic development, the induction of this antigen at inappropriate times might provide one mechanism whereby intrauterine infection with HCMV can damage the developing fetal nervous system.

Antigens, Viral↗