PubMed Health⌕ Search

Biomedical subjects

D Slonim

Publications and source records attributed to D Slonim.

At least 19 recordsLinked to original sources

[Global eradication of poliomyelitis. On the 80th anniversary of the founding of the National Institute of Health].

Global eradication of poliomyelitis launched and coordinated by the World Health Organization since 1988 is close to being achieved: the main objective is to discontinue the circulation of the wild, neurovirulent, endemic virus of poliomyelitis. Although this objective has been within the reach, there are two other risks, lower but existing and posing possible threat to the eradication, that need to be controlled: 1) wild polioviruses stored in laboratories should be destroyed or reliably contained and 2) emergence and epidemic role of neurovirulent polioviruses potentially derived from attenuated oral polio vaccine should be prevented. After all these global eradication objectives are met and three years relapse from its certification, under intensive and sensitive surveillance, it will be possible to consider whether or not to stop vaccination against poliomyelitis in the world. The global eradication of poliomyelitis is a complex issue that will require further efforts in the field of both the biomedical research and organizational, economic and political approaches. In the Czech Republic, poliomyelitis has been eradicated since 1960. The former Czechoslovakia was the first country in the world to achieve and to scientifically demonstrate nationwide eradication of poliomyelitis. The current post-eradication surveillance of poliomyelitis in the Czech Republic is managed by the Centre of Epidemiology and Microbiology of the National Institute of Public Health in cooperation with the Ministry of Health of the Czech Republic, WHO Regional Office for Europe in Copenhagen and National Certification Committee for Poliomyelitis Eradication.

Czech Republic↗

Detection of antibodies to polyomavirus SV40 in two central European countries.

Simian virus 40 (SV40) is significantly associated with some human cancers. However, the frequency of tumor-associated virus detection differs by geographic regions, so it is important to understand the status of SV40 infections in different populations. Poliovaccines potentially containing live SV40 were used in well-documented nationwide vaccination programs in Hungary and the Czech Republic that are reported here. We analyzed serum samples from periodic surveillance programs in those two countries for antibodies to SV40 using a specific plaque reduction neutralization assay. The prevalence of antibodies was between 1.3 and 8.7% in Hungary and from 1.0 to 4.0% in the Czech Republic. Females had a higher rate of antibodies than males, reaching in certain age groups 15.6% in Hungary and 8.3% in the Czech Republic. Antibodies to SV40 were found in similar proportions in both countries among persons not directly exposed to poliovaccines and subjects vaccinated in the era of SV40-free vaccines. Complexities and limitations of current serological approaches to epidemiological studies of SV40 in humans are discussed. These data suggest that SV40 may be present in these populations and emphasize the importance of follow-up studies to determine the pathogenesis of infections by this emerging human agent.

Adolescent↗

Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks.

In an effort to find gene regulatory networks and clusters of genes that affect cancer susceptibility to anticancer agents, we joined a database with baseline expression levels of 7,245 genes measured by using microarrays in 60 cancer cell lines, to a database with the amounts of 5,084 anticancer agents needed to inhibit growth of those same cell lines. Comprehensive pair-wise correlations were calculated between gene expression and measures of agent susceptibility. Associations weaker than a threshold strength were removed, leaving networks of highly correlated genes and agents called relevance networks. Hypotheses for potential single-gene determinants of anticancer agent susceptibility were constructed. The effect of random chance in the large number of calculations performed was empirically determined by repeated random permutation testing; only associations stronger than those seen in multiply permuted data were used in clustering. We discuss the advantages of this methodology over alternative approaches, such as phylogenetic-type tree clustering and self-organizing maps.

Antineoplastic Agents↗

Evaluation of predictive factors for neurocognitive dysfunction in patients with inactive systemic lupus erythematosus.

OBJECTIVE: To determine predictive factors associated with the cognitive dysfunction in patients with inactive systemic lupus erythematosus (SLE). METHODS: Consecutive patients followed at the Lupus Clinic with inactive SLE (SLE Disease Activity Index, SLEDAI, = 0) underwent a battery of neuropsychological tests; Beck Depression Inventory and psychiatric assessment were also performed. Neurocognitive dysfunction was defined as 3 abnormal scores. Data were analyzed using chi-square tests, ANOVA tests, and logistic regression. RESULTS: Twenty-five of the 58 patients with SLE (43%) versus 9 of 47 healthy controls (19%) demonstrated neurocognitive dysfunction (p < 0.01). Neurocognitive dysfunction was not associated with depression or a psychiatric diagnosis, use of steroids, or previous or current evidence for fibromyalgia. SLEDAI > 10 at first presentation to the Lupus Clinic and previous vasculitis were associated with neurocognitive dysfunction, but previous central nervous system disease, renal disease, renal damage, or atherosclerotic complications were not. Neurophysiologic studies at the time of the assessment were not predictive of neurocognitive dysfunction. CONCLUSION: Patients with inactive SLE demonstrate neurocognitive dysfunction. This is associated with more disease activity at presentation, but is not associated with specific organ involvement or organ damage.

Adult↗

Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation.

Array technologies have made it straightforward to monitor simultaneously the expression pattern of thousands of genes. The challenge now is to interpret such massive data sets. The first step is to extract the fundamental patterns of gene expression inherent in the data. This paper describes the application of self-organizing maps, a type of mathematical cluster analysis that is particularly well suited for recognizing and classifying features in complex, multidimensional data. The method has been implemented in a publicly available computer package, GENECLUSTER, that performs the analytical calculations and provides easy data visualization. To illustrate the value of such analysis, the approach is applied to hematopoietic differentiation in four well studied models (HL-60, U937, Jurkat, and NB4 cells). Expression patterns of some 6,000 human genes were assayed, and an online database was created. GENECLUSTER was used to organize the genes into biologically relevant clusters that suggest novel hypotheses about hematopoietic differentiation-for example, highlighting certain genes and pathways involved in "differentiation therapy" used in the treatment of acute promyelocytic leukemia.

Animals↗

A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat.

The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP x BN and FHH x ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod >/= 3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. (1997); James and Tanigami, RHdb (http:www.ebi.ac.uk/RHdb/index.html); Wilder (http://www.nih.gov/niams/scientific/ratgbase); Serikawa et al. (1992); RATMAP server (http://ratmap.gen.gu.se)] RH maps (v. 2.0) have been posted on our web sites at http://goliath.ifrc.mcw.edu/LGR/index.html or http://curatools.curagen.com/ratmap. Both web sites provide an RH mapping server where investigators can localize their own RH vectors relative to this map. The raw data have been deposited in the RHdb database. Taken together, these maps provide the basic tools for rat genomics. The RH map provides the means to rapidly localize genetic markers, genes, and ESTs within the rat genome. These maps provide the basic tools for rat genomics. They will facilitate studies of multifactorial disease and functional genomics, allow construction of physical maps, and provide a scaffold for both directed and large-scale sequencing efforts and comparative genomics in this important experimental organism.

Alleles↗

Building human genome maps with radiation hybrids.

Genome maps are crucial tools in human genetic research, providing known landmarks for locating disease genes and frameworks for large-scale sequencing. Radiation hybrid mapping is one technique for building genome maps. In this paper, we describe the methods used to build radiation hybrid maps of the entire human genome. We present the hidden Markov model that we employ to estimate the likelihood of a map despite uncertainty about the data, and we discuss the problem of searching for maximum-likelihood maps. We describe the graph algorithms used to find sparse but reliable initial maps and our methods of extending them. Finally, we show results validating our software on simulated data, and we describe our genome-wide human radiation hybrid maps and the evidence supporting them.

Chromosome Mapping↗

Pattern of neuropsychologic dysfunction in inactive systemic lupus erythematosus.

The pattern of neuropsychological dysfunction in patients with inactive systemic lupus erythematosus (SLE) was examined. Fifty-eight subjects with inactive SLE and 47 healthy controls were administered a standardized neuropsychological test battery. Summary scores reflecting 18 different cognitive processes were derived. Subjects were designated cognitively impaired if three or more summary scores differed significantly from premorbid estimates of cognitive functioning. Cognitive impairment was identified in 43% of subjects with inactive SLE and 19% of healthy controls. Subjects with inactive SLE, as a group, performed significantly worse than healthy controls on measures of auditory verbal memory, visual spatial memory, psychomotor speed, and motor functioning. A significantly greater proportion of subjects with inactive SLE than healthy controls was impaired only on a measure of visual spatial memory. Cognitive impairment in subjects with inactive SLE was associated with increasing age. There were no associations between cognitive impairment and current depressive symptoms or current corticosteroid use. These findings suggest that cognitive dysfunction occurs frequently in inactive SLE. The variability of performance of subjects with inactive SLE is consistent with the heterogeneity of CNS involvement in the disease.

Adult↗

History of poliomyelitis in the Czech Republic--Part III.

The "repression phase" of paralytic poliomyelitis in the Czech Republic (and in the Slovak Republic as well) between 1957 and 1960 was characterized by controlled, short term, mass vaccination campaigns. In spring 1957, at the very beginning of a polio epidemic, about 87% of all children aged 1 to 7 years and about 40% of those aged 8 to 15 years were intradermally vaccinated with IPV. The protective effect in population given two IPV doses was 66% (in Slovakia 74%). The starting epidemic of 1957 was stopped. Morbidity and mortality from poliomyelitis markedly decreased in 1958. Nevertheless, about 39%, 13% and 41% of children aged under 8 years (given three IPV doses) had not specific virus-neutralizing antibodies against polioviruses types 1, 2 and 3 respectively. A field trial with OPV started in winter 1958-59. Over 110,000 children aged 2 to 6 years were vaccinated with Sabin OPV, which proved to be safe, highly immunogenic and protective. In spring 1960 about 93% of children were vaccinated in the former Czechoslovakia with OPV in a mass, countrywide campaign. No case of paralytic poliomyelitis was reported during the second half of 1960. The same was true for all year 1961, the first year of the historical period of poliomyelitis elimination in our country.

Czech Republic↗

A history of poliomyelitis in the Czech Republic--Part II.

The first large epidemic of poliomyelitis in (previous) Czechoslovakia was recorded in 1939. It affected only the western part of the state, Bohemia, with a relatively high morbidity and mortality, 25.42 and 2.05 per 100,000, respectively, the death rate being 8.1%. In Prague, children aged between 5 and 9 years represented 41.5% and those up to 14 years 84% of all cases of poliomyelitis. Other epidemics followed in 1943, 1948 and 1953 affected Moravia and Slovakia as well. The highest death rates were in the interepidemic periods, the lowest ones were recorded in the epidemics. During the "epidemic phase" between 1939 and 1956, 12,868 cases of poliomyelitis and 1,159 deaths from poliomyelitis were reported, the mean death rate value being 9.0%. General hygiene measures, passive immunization with specific convalescent human sera and intranasal "chemoprophylaxis" tried then on a large scale, did not show any demonstrable antiepidemic effect.

Adolescent↗

A history of poliomyelitis in the Czech Republic--Part I.

The incidence of poliomyelitis in the Czech Republic shows four epidemiologically different phases recorded during a lifetime of one human generation: endemicity (until 1938), epidemicity (1939 to 1956), repression (1957 to 1960) and elimination (1961 till now). The phase of the endemic incidence of poliomyelitis studied in this paper finished in 1938. Since 1919 when poliomyelitis notification was started, three waves of increasing though low mortality were observed: in 1926, 1932 and 1936 (0.27, 0.43 and 0.38 per 100,000, respectively). Between 1919 and 1938 the mortality increased in children over one year but it remained relatively highest in infants under one year of age. The poliomyelitis death rates were high between 1928 and 1938, 23.6% on the average. Such high rates might be attributable to the underrated morbidity cases in comparison with a rather reliably notified polio mortality. The period between 1919 and 1938 represented the end of the endemic incidence of poliomyelitis in the Czech countries, and it could be considered as preepidemic.

Czech Republic↗

A recombinant vaccinia virus expressing hepatitis B virus middle surface protein. Restricted expression of HBV antigens in human diploid cells.

Several vaccinia virus recombinants inducing the synthesis of the middle surface (M) protein of hepatitis B virus (HBV) were constructed. One of them, denoted v137, was examined in some detail. The virus replicated nearly to the same extent in various cell lines, viz. human embryo diploid fibroblast LEP and MRC-5 cells, rabbit embryo fibroblast REF cells, TK- rat RAT-2 cells, and green monkey CV-1 cells. However, the production of M protein was found considerably lower in the human LEP and MRC-5 than in the other cells examined. In addition, the kinetics of M formation were different in these two cell systems, LEP cells lagging significantly behind CV-1 cells. The low-level production of M protein in LEP cells was not increased by repeated v137 passages in LEP cells, nor by a passage in a laboratory worker accidentally infected with the v137 virus, nor by shortening the leader sequence preceding the translation initiation codon. The greater part of the M antigen was found to be cell associated, more so in the cells of human than monkey origin. From the major HBV S antigen (HBsAg) isolated from the plasma of chronically infected subjects, the antigen released by cell destruction differed by binding to polymerized human albumin. This property was utilized in ELISA to detect anti-preS2 antibody. Rabbits inoculated intradermally with the v137 virus developed antibodies reactive in this assay as well as with a synthetic peptide corresponding in the amino acids 14-34 of the NH2 terminus of the HBsAg preS2 region.

Animals↗

Biochemical properties of monoamine-rich human neuroblastoma cells.

The biochemical, pharmacological and immunological characterization of cells derived from human neuroblastoma tumors recently acquired great interest, since these cells may be a putative donor source for transplantation in animal models of neurological disorders. We measured monoamine levels, tyrosine hydroxylase (TH) immunostaining, and the expression of major histocompatibility cell surface antigens (MHC) in 7 human neuroblastoma cell lines. Three cell lines (LAN5, NB69 and CHP126) had high levels of monoamines. TH immunostaining was strongly positive in CHP126 and LAN5, and NB69. MHC were not detected in any of the cells with high catecholamine levels. Treatment with neuroleptics increased the metabolism of dopamine in LAN5 but not in NB69. The implantation of LAN5 cells in immunocompetent, unilaterally 6-hydroxydopamine-lesioned rats decreased the apomorphine-induced contralateral rotation. The effect of the implant was greatest in animals in which LAN5 neuroblastoma cells, pretreated with dibutyryl cyclic adenosine monophosphate (DBcAMP) and prostaglandin E1 (PGE1, were implanted into the cerebral ventricle ipsilateral to the lesion, and then irrigated with DBcAMP administered through a totally implanted drug delivery system. The effect of the implant decreased after the second week. Neuroblastoma cells were found in approximately 50% of the implanted animals. TH immunostaining was weak or absent in the grafted animals. Inflammatory changes were present in the majority of the brains examined. Extensive tumor growth was present in one animal implanted with untreated cells. Grafting of cells treated with DBcAMP and PGE1 plus with mitomycin C and bromodeoxyuridine in animals immunosuppressed with cyclosporin A reduced the apomorphine-induced rotation to 40-60% of baseline levels and this reduction persisted beyond the period of infusion with DBcAMP. Intraventricular infusion of DBcAMP in animals injected with cell culture medium produced a transient reduction of rotation to 70% of baseline. The amphetamine-induced rotation was not significantly reduced during the 4 weeks follow up. Atypical cells, consistent with surviving neuroblastoma cells, were observed in the brain of all transplanted animals. TH immunostaining was weak or negative in most cases. Human neuroblastoma cells may be an alternative donor tissue for the study of the effects of transplantation in animal models of Parkinson's disease.

Animals↗

Increasing incidence and excellent survival of patients with early gastric cancer: experience in a United States medical center.

PURPOSE: In Japan, early gastric cancer has an excellent survival rate. In the United States, the disease is less well understood, and it is viewed more pessimistically, although we have previously shown in a small series of patients good short-term survival rates in early gastric cancer as compared with advanced gastric cancer. Our purpose in this study was to determine if the incidence of early gastric cancer and the associated survival rate has changed over a 24-year period. PATIENTS AND METHODS: From the records at the Columbia Presbyterian Medical Center, 549 patients were identified who underwent gastric resection for cancer between 1960 and 1984, 69 of whom had early gastric cancer. Survival data were obtained in 63 patients. A comparison of survival rates was conducted between patients with early gastric cancer and the 1980 census figures. RESULTS: Over the 24-year period, the total number of resections for gastric cancer at our institution declined. However, the percentage of gastric resections that satisfied the Japanese criteria for early gastric cancer increased from 9 percent between 1960 to 1974 to 17 percent between 1975 to 1984 (p less than 0.05). Of the 69 early gastric cancers, 35 percent involved the mucosa, whereas in 65 percent the malignancy invaded the submucosa. Twenty-eight percent had lymph node involvement. For the patients for whom survival data were available, survival was better than the 1980 census (p less than 0.05). The adjusted five-year survival rate was 97 percent. Neither submucosal invasion nor lymph node involvement altered survival. Patients with type III early cancers (ulcerated), however, had a significantly greater survival rate than patients with type I (polypoid) early cancers (p less than 0.05). CONCLUSION: Early gastric cancer is being diagnosed with increasing frequency and has an excellent survival rate. These findings are similar to the Japanese experience and argue for an ongoing aggressive approach to endoscopic biopsy of gastric lesions.

Aged↗

Detection of postvaccination mumps virus antibody by neutralization test, enzyme-linked immunosorbent assay and sensitive hemagglutination inhibition test.

A group of 251 children aged 2-3 years given live attenuated mumps virus vaccine PAVIVAC of Czechoslovak production were tested for antiparotitis antibody levels in pre- and postvaccination sera by neutralization test (NT), enzyme-linked immunosorbent assay (ELISA) and sensitive hemagglutination inhibition test, enhanced by heterologous antibody to human immunoglobulin G (E-HIT). The prevaccination findings were as follows: positive ELISA IgG titres, neutralization antibodies and hemagglutination inhibition antibodies were present in, respectively, 35%, 25.9% and 27.9% of the sera. Postvaccination seroconversions were evaluated in 159 susceptible vaccinees whose prevaccination sera had been negative by all three tests. The lowest seroconversion was detected by NT (74.2%), seroconversions by ELISA and E-HIT were appreciably higher (82.4% and 86.8%, respectively). The seven children showing a seroconversion by E-HIT but not by ELISA had a 4 fold increase of anti-mumps ELISA IgG antibodies as well, but the rise of antibody titres was at a level falling in the range below the positivity criterion for ELISA. The statistically evaluated detection rate for antibodies was significantly higher (significance test "t") by ELISA as compared with neutralization test. However, antibody levels (geometric mean titres) were 8-10 times lower in postvaccination sera than in convalescent sera of 30 children with mumps in all three tests.

Antibodies, Viral↗