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J S Smith

Publications and source records attributed to J S Smith.

At least 73 records · Page 4Linked to original sources
PubMed2000

Mammalian reservoirs and epidemiology of rabies diagnosed in human beings in the United States, 1981-1998.

Between 1981 and 1998, 37 cases of rabies were diagnosed in human beings in the United States. Information directly linking the cause of infection to animal bite was available for only eight of these cases. Indirect incrimination of the vector by analysis of cDNA sequences obtained by reverse transcriptase polymerase chain reaction of samples indicated that for all cases (12/12) believed to have been acquired in foreign countries, variants of the rabies virus (VRVs) associated with dogs (7/12 involved known bite histories) were the cause of the rabies infections. In contrast, VRVs associated with bats (bat-associated VRVs or BAVs) were implicated as the cause of 88% (22/25) of infections believed to have been acquired within the United States (1/22 involved known bite histories). Sequence analyses revealed that a single BAV (Ln/Ps), associated with rabid silver-haired (Lasionycteris noctivagans) and Eastern pipistrelle (Pipistrellus subflavus) bats, was implicated in 73% (16/22) of bat-associated infections. Silver-haired bats are predominantly solitary and migratory. Eastern pipistrelle bats may occur individually or in small clusters. Both species are only infrequently submitted for rabies testing. Unrecognized bites and unique properties of the Ln/Ps BAV may explain its association with the majority of rabies infections in human beings in the United States.

Animals↗
PubMed2000

Molecular epidemiology of rabies virus isolates from Israel and other middle- and Near-Eastern countries.

A total of 226 isolates of rabies virus from different areas of Israel, including three human isolates and one sample from South Lebanon were identified between 1993 and 1998 by direct immunofluorescence using monoclonal antibodies to the viral nucleoprotein (N). An epidemiological survey based on nucleotide sequence analysis of 328 bp from the C terminus of the N coding region and the noncoding region between the nucleoprotein and the phosphoprotein (NS gene) was performed. Phylogenetic analysis of the isolates from Israel showed that they were related geographically, but not according to host species. Five variants, related groups distributed among four geographical regions, were identified. In each region, rabies virus was isolated from more than one animal species. A comparison of the sequence analysis of rabies virus samples from the rest of world revealed a 2-nucleotide change that distinguished the Middle East variants from the rest.

Adult↗
PubMed2000

Effects of the novel NMDA receptor antagonist gacyclidine on recovery from medial frontal cortex contusion injury in rats.

Gacyclidine, a novel, noncompetitive NMDA receptor antagonist, was injected (i.v.) into rats at three different doses to determine if the drug could promote behavioral recovery and reduce the behavioral and anatomical impairments that occur after bilateral contusions of the medial frontal cortex (MFC). In the Morris water maze, contused rats treated with gacyclidine at a dosage of 0.1 mg/kg performed better than their vehicle-treated conspecifics. Rats given gacyclidine at either 0.3 or 0.03 mg/kg performed better than brain-injured controls, but not as well as those treated with 0.1 mg/kg. Counts of surviving neurons in the nucleus basalis magnocellularis (NBM) and the medial dorsal nucleus (MDN) of the thalamus were used to determine whether gacyclidine treatment attenuated secondary cell death. In both the NBM and the MDN, the counts revealed fewer surviving neurons in untreated contused rats than in gacyclidine-treated rats. Increases in the size and number of microglia and astrocytes were observed in the striatum of gacyclidine-treated contused brains. Although most consequences of MFC contusions were attenuated, we still observed increases in ventricle dilation and thinning of the cortex. In fact, the ventricles of rats treated with 0.1 mg/kg of gacyclidine were larger than those of their vehicle treated counterparts, although we observed no behavioral impairment.

Animals↗
PubMed2000

Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas.

PURPOSE: A recent report suggests that alterations of chromosome arms 1p and 19q are associated with chemotherapeutic response and overall survival in anaplastic oligodendroglioma patients treated with procarbazine, lomustine, and vincristine chemotherapy. We set out to further clarify the diagnostic and prognostic implications of these alterations in a broader set of diffuse gliomas, including astrocytic neoplasms and low-grade oligodendrogliomas. PATIENTS AND METHODS: Fluorescence in situ hybridization (FISH) signals from DNA probes mapping to 1p and 19q common deletion regions were enumerated in 162 diffuse gliomas (79 astrocytomas, 52 oligodendrogliomas, and 31 mixed oligoastrocytomas), collected as part of an ongoing prospective investigation of CNS tumors. RESULTS: The oligodendroglial phenotype was highly associated with loss of 1p (P =.0002), loss of 19q (P <.0001), and combined loss of 1p and 19q (P <.0001). Combined loss of 1p and 19q was identified as a univariate predictor of prolonged overall survival among patients with pure oligodendroglioma (log-rank, P =.03) and remained a significant predictor after adjusting for the effects of patient age and tumor grade (P <.01). This favorable association was not evident in patients with astrocytoma or mixed oligoastrocytoma. CONCLUSION: Combined loss of 1p and 19q is a statistically significant predictor of prolonged survival in patients with pure oligodendroglioma, independent of tumor grade. Given the lack of this association in patients with astrocytic neoplasms and the previously demonstrated chemosensitivity of oligodendrogliomas, a combined approach of histologic and genotypic assessment could potentially improve existing strategies for patient stratification and management.

Adolescent↗
PubMed2000

Effects of modified tall oil versus a commercial source of conjugated linoleic acid and increasing levels of modified tall oil on growth performance and carcass characteristics of growing-finishing pigs.

Two experiments were conducted to evaluate the effects of conjugated linoleic acid (CLA)-enriched feed additives for swine. These additives included a source of CLA that was commercially available (CLA-60) and modified tall oil (MTO). Experiment 1 used 36 barrows (initially 37.6+/-2.8 kg) to compare the effects of CLA-60 and MTO on growth performance and carcass characteristics of finishing pigs. The corn-soybean meal diets contained .50% soybean oil (control), .50% CLA-60, or .50% MTO. Pigs fed CLA-60 had less (P = .03) ADG from 37.6 to 72.6 kg than the control pigs; otherwise, pigs fed either CLA-60 or MTO had growth performance similar (P > .15) to that of the control pigs. Pigs fed MTO grew faster (P = .03) and consumed more feed (P = .10) over the duration of the experiment (37.6 to 106.4 kg) than pigs fed CLA-60. Dietary treatment did not affect (P > .15) plasma triglycerides or carcass characteristics, but pigs fed either MTO or CLA-60 had greater saturation of fatty acids in the adipose tissue at the 10th rib than pigs fed the control diet. Experiment 2 used 80 barrows (initially 33.4+/-2.2 kg) to examine the effects of increasing levels of MTO on growth performance and carcass characteristics of finishing pigs. The corn-soybean meal diet contained 1% cornstarch, which was replaced with MTO to give dietary levels of .25, .50, or 1.00% MTO. Dietary treatment did not affect (P > .15) growth performance. Feeding increasing levels of MTO quadratically decreased (P = .02) average backfat thickness and longissimus muscle drip loss (P = .04) and quadratically increased longissimus muscle area (P = .07) and percentage lean (P = .03). Feeding MTO tended to increase belly firmness (P < .10) compared with pigs fed the control diet. These traits appeared to be optimized with .50% MTO. In summary, pigs fed MTO had greater ADG, ADFI, and ending BW than pigs fed CLA-60. Feeding MTO does not appear to affect growth performance but improves carcass lean content and may additionally improve some aspects of meat quality in growing-finishing pigs.

Adipose Tissue↗
PubMed1999

Rabies surveillance in the United States during 1998.

During 1998, 49 states, the District of Columbia, and Puerto Rico reported 7,961 cases of rabies in nonhuman animals and 1 case in a human being to the Centers for Disease Control and Prevention, a decrease of 6.5% from 8,509 cases in nonhuman animals and 4 cases in human beings reported in 1997. More than 92% (7,358 cases) were in wild animals, whereas > 7.5% (603 cases) were in domestic species (compared with 93% in wild animals and 7% in domestic species in 1997). Decreases were evident in all of the major contributing species groups, with the exception of skunks and bats. The relative contributions of the major groups to the total reported for 1998 were reccoons (44.0%; 3,502 cases), skunks (28.5%; 2,272), bats (12.5%; 992), foxes (5.5%; 435), cats (3.5%; 282), cattle (1.5%; 116), and dogs (11.5%; 113). No further discernable westward extension of the epizootic of rabies in raccoons in Ohio was reported. Twelve of the 19 states enzootic for the raccoon variant of the rabies virus and the District of Columbia reported decreased numbers of cases of rabies during 1998, compared with 13 states and the District of Columbia that reported increases during 1997. Three states, Rhode Island (143.2%), Massachusetts (77.2%), and New Hampshire (69.4%), reported increases of > 50% during 1998, compared with totals reported for 1997. In Texas, the number of cases of rabies associated with enzootic canine variants of the rabies virus remained greatly diminished; however, overall totals of reported cases of rabies increased in Texas and 12 other states where skunks are the major terrestrial reservoir of rabies. At the national level, the total of 82 reported cases of rabies among horses and mules was greater than that reported for any year since 1981 (88 cases) and represented a 74.5% increase, compared with the total for 1997. The 992 cases of rabies reported in bats during 1998 were the greatest proportionate contribution by bats since 1990. Reported cases of rabies in cats (282), dogs (113), and cattle (116) decreased 6.0%, 10.3%, and 4.9%, respectively. One indigenously acquired case of rabies reported in a human being during 1998 was the result of infection with a rabies virus variant associated with silver-haired and eastern pipistrelle bats.

Animals↗
PubMed1999

Redirected infection of directly biotinylated recombinant adenovirus vectors through cell surface receptors and antigens.

The inability of adenovirus to infect primitive hematopoietic cells presents an obstacle to the use of adenovirus vectors for gene transfer to these cell types. Therefore, expanding the tropism of adenovirus vectors to unique cell surface antigens would be an important development for gene therapy protocols. In this study, we sought to redirect infection of adenovirus vectors to primitive human hematopoietic cells that universally express the c-Kit receptor on their cell surface. To accomplish this, a vector was constructed by covalently linking biotin molecules to recombinant adenovirus, followed by addition of the biotinylated ligand for the c-Kit receptor, stem cell factor (SCF), through an avidin bridge. Gene transfer was directed specifically to c-Kit-positive hematopoietic cell lines, resulting in up to a 2,440-fold increase in luciferase expression with frequencies equivalent to recombinant virus infection of permissive cells. Substitution of biotinylated antibodies directed against c-Kit, CD34 (binds L-selectin), and CD44 (hyaluronate receptor) receptors for biotinylated SCF resulted in 50-, 8-, and 260-fold increases in reporter gene expression, respectively, demonstrating that infection also could be redirected through antibody-antigen interactions and through antigens other than growth factor receptors. The versatility of this vector was demonstrated further by infection of primary T cells with vectors targeted with antibodies to CD44 (resting and activated T cells) and biotinylated IL-2 (activated T cells only). Taken together, directly biotinylated adenovirus vectors represent a versatile and efficient method for redirection of virus infection to specific cells.

Adenoviruses, Human↗
PubMed1999

Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype.

Allelic alterations of chromosomes 1 and 19 are frequent events in human diffuse gliomas and have recently proven to be strong predictors of chemotherapeutic response and prolonged survival in oligodendrogliomas (Cairncross et al., 1998; Smith et al., submitted). Using 115 human diffuse gliomas, we localized regions of common allelic loss on chromosomes 1 and 19 and assessed the association of these deletion intervals with glioma histological subtypes. Further, we evaluated the capacity of multiple modalities to detect these alterations, including loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH). The correlation coefficients for detection of 1p and 19q alterations, respectively, between modalities were: 0.98 and 0.87 for LOH and FISH, 0.79 and 0.60 for LOH and CGH, and 0.79 and 0.53 for FISH and CGH. Minimal deletion regions were defined on 19q13.3 (D19S412-D19S596) and 1p (D1S468-D1S1612). Loss of the 1p36 region was found in 18% of astrocytomas (10/55) and in 73% (24/33) of oligodendrogliomas (P < 0.0001), and loss of the 19q13.3 region was found in 38% (21/55) of astrocytomas and 73% (24/33) of oligodendrogliomas (P = 0.0017). Loss of both regions was found in 11% (6/55) of astrocytomas and in 64% (21/33) of oligodendrogliomas (P < 0.0001). All gliomas with LOH on either 1p or 19q demonstrated loss of the corresponding FISH probe, 1p36 or 19q13.3, suggesting not only locations of putative tumor suppressor genes, but also a simple assay for assessment of 1p and 19q alterations as diagnostic and prognostic markers.

Astrocytoma↗
PubMed1999

Regional changes in the expression of neurotrophic factors and their receptors following acute traumatic brain injury in the adult rat brain.

We have analyzed the effect of severe traumatic brain injury (TBI) on the levels of mRNA expression of neurotrophic factors (NTFs): brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) and their respective receptors: trkB, trkA and CNTFRalpha. The expression was examined in the region of the lesion as well as a region remote from the lesion at 12, 24, and 36 h following the injury. Our data suggest that after the brain injury, the expression of NGF and BDNF mRNAs were early, transiently and significantly upregulated while that of CNTF was a slow and less amplified response in both areas of the brain. We also found that trkA mRNA expression was only upregulated significantly in the remote area; trkB mRNA showed no significant change in either area except an upregulation at 12 h in the remote area. CNTFRalpha was downregulated significantly by 24-36 h in the lesion area and by 24 h in the remote area. These changes suggest that TBI regulates the expression of NTFs and their receptors. These alterations in expression may be involved in modulating the neuronal response after brain injury.

Age Factors↗
PubMed1999

Cloning of a human ortholog (RPH3AL) of (RNO)Rph3al from a candidate 17p13.3 medulloblastoma tumor suppressor locus.

Allelic loss of 17p13.3 is observed in approximately 40% of medulloblastomas, suggesting the presence of a tumor suppressor gene in this region. Deletion mapping has defined a region of common loss flanking the telomeric marker D17S34, and a recent report delineated a 9-kb homozygous deletion within the D17S34 locus in one such tumor. Using cDNA selection, we have identified a transcript spanning this deletion, designated (HSA)RPH3AL (rabphillin-3A-like), based on its 77% overall amino acid identity with a recently cloned rat gene, (RNO)Rph3al (originally termed Noc2), a gene putatively involved in regulated endocrine exocytosis through its interactions with the cytoskeleton. We determined the exon-intron boundaries of RPH3AL and screened the coding region for mutations by direct sequencing in DNA extracted from 33 tumor samples with allelic loss of 17p13, including 10 medulloblastoma, 14 follicular thyroid cancer (FTC), and 9 ovarian cancer specimens. No mutations were identified. Thus, despite its location in a homozygously deleted 17p13.3 locus, it is unlikely that RPH3AL is a gene involved in the oncogenesis of medulloblastoma, FTC, or ovarian cancer.

Adaptor Proteins, Signal Transducing↗
PubMed1999

The human glia maturation factor-gamma gene: genomic structure and mutation analysis in gliomas with chromosome 19q loss.

Human glia maturation factor-gamma (hGMF-gamma) is a recently identified gene that may be involved in glial differentiation, neural regeneration, and inhibition of tumor cell proliferation. The gene maps to the long arm of chromosome 19 at band q13.2, a region that is frequently deleted in human malignant gliomas and is thus suspected to harbor a glioma tumor suppressor gene. Given the putative role of hGMF-gamma in cell differentiation and proliferation and its localization to chromosome 19q13, this gene is an interesting candidate for the chromosome 19q glioma tumor suppressor gene. To evaluate this possibility, we determined the genomic structure of human hGMF-gamma and performed mutation screening in a series of 41 gliomas with and without allelic loss of chromosome 19q. Mutations were not detected, which suggests that hGMF-gamma is not the chromosome 19q glioma suppressor gene. However, the elucidation of the genomic structure of hGMF-gamma may prove useful in future investigations of hGMF-gamma in the normal adult and developing human nervous system.

Adult↗
PubMed1999

Typing of rabies virus isolates by DNA enzyme immunoassay.

BACKGROUND: Alternatives to antigenic typing are needed for epidemiologic surveys of the rabies virus associated with translocated coyotes and foxes, especially in areas where a closely related rabies virus is transmitted by striped skunks. OBJECTIVES: We developed and evaluated two enzyme based typing methods for rabies virus. The products of a reverse transcription-polymerase chain reaction (RT/PCR) of the nucleoprotein gene were hybridized to type specific probes and detected by enzyme assay after immobilization on microtiter plates. STUDY DESIGN: We tested RT/PCR products of 27 rabies isolates by two different DNA enzyme immunoassays (DEIA) and evaluated the quality of the results from the corresponding nucleotide sequence of the samples. RESULTS: Using a set of two probes, one of the DEIAs correctly identified 26/27 samples as variants of rabies virus associated with either skunks, foxes, or coyotes. The identity of one fox rabies sample was unresolved by this assay. The second DEIA correctly identified 24/27 samples as variants of rabies virus associated with either skunks, foxes, or coyotes. This assay did not resolve the identity of two fox rabies samples, and misidentified one fox rabies sample as a skunk rabies sample. CONCLUSIONS: DEIA can be used for epidemiologic studies of variants of rabies virus associated with skunks, foxes, and coyotes. Both DEIA methods were effective when typing probes recognized changes at a minimum of two nucleotide positions between variants, but only one assay method was sufficiently stringent to detect a single base pair mismatch. The inherent mutability of RNA viruses must be considered when designing and evaluating typing methods.

Animals↗
PubMed1999

A quantitative analysis of factors affecting PELs and TLVs for carcinogens.

For carcinogens, this paper provides a quantitative examination of the roles of potency and weight-of-evidence (WOE) in setting permissible exposure limits (PELs) at the U.S. Occupational Safety and Health Administration (OSHA) and threshold limit values (TLVs) at the private American Conference of Governmental Industrial Hygienists (ACGIH). On normative grounds, both of these factors should influence choices about the acceptable level of exposures. Our major objective is to examine whether and in what ways these factors have been considered by these organizations. A lesser objective is to identify outliers, which might be candidates for further regulatory scrutiny. Our sample (N = 48) includes chemicals for which EPA has estimated a unit risk as a measure of carcinogenic potency and for which OSHA or the ACGIH has a PEL or TLV. Different assessments of the strength of the evidence of carcinogenicity were obtained from EPA, ACGIH, and the International Agency for Research on Cancer. We found that potency alone explains 49% of the variation in PELs and 62% of the variation in TLVs. For the ACGIH, WOE plays a much smaller role than potency. TLVs set by the ACGIH since 1989 appear to be stricter than earlier TLVs. We suggest that this change represents evidence that the ACGIH had responded to criticisms leveled at it in the late 1980s for failing to adopt sufficiently protective standards. The models developed here identify 2-nitropropane, ethylene dibromide, and chromium as having OSHA PELs significantly higher than predicted on the basis of potency and WOE.

Carcinogens↗
PubMed1999

Bioelectrical impedance plethysmographic analysis of body composition in critically injured and healthy subjects.

BACKGROUND: Determination of body composition during critical illness is complex because of various patient-related and technical factors. Bioelectrical impedance is a promising technique for the analysis of body composition; however, its clinical utility in critically injured patients is unknown. OBJECTIVE: The purpose of this study was to compare bioelectrical impedance with metabolic activity in healthy and critically injured patients. If bioelectrical impedance accurately determines body composition during critical illness, the slope between body-composition variables and oxygen consumption would be the same in critically injured and healthy subjects. DESIGN: There is a strong linear relation between body composition and metabolic activity. In the present study, body composition (fat-free mass and body cell mass) was determined by using bioelectrical impedance and resting metabolic activity (metabolic rate and oxygen consumption) by using gas exchange analysis in a group of healthy and critically injured subjects. The relation between these variables was compared by using linear regression to a similar relation established by hydrostatic weighing in a large historical control group. RESULTS: The slope of the line relating fat-free mass to resting metabolic rate was the same in the healthy and critically ill groups (P = 0.62) and each was similar to the slope of the line for the control group. However, in 37% of the critically injured group, overhydration contributed to an increase in fat-free mass, disturbing the relation with resting metabolic rate. The slope of the line relating body cell mass to oxygen consumption in our healthy and critically ill groups was almost identical. CONCLUSION: These results support the use of bioelectrical impedance to determine body cell mass in healthy and critically ill subjects.

Adult↗
PubMed1999

Quantification of delta-opioid receptors in human brain with N1'-([11C]methyl) naltrindole and positron emission tomography.

The regional binding of N1'-([11C]methyl)naltrindole (MeNTI), a selective delta-opioid antagonist, was studied in healthy human subjects with positron emission tomography (PET). After the bolus intravenous administration of high specific activity [11C]MeNTI, PET was performed over 90 minutes. Arterial plasma samples were obtained during the scanning period and assayed for the presence of radiolabeled metabolites. The data were analyzed with various kinetic (two- and three-compartment models, Patlak graphical analysis) and nonkinetic (apparent volume of distribution and activity at a late scanning time) approaches. This tracer showed irreversible binding characteristics during the scanning period used. The results of the analyses also were compared with the density and distribution of delta-opioid receptors in the human brain in vitro. Additionally, computer simulations were performed to assess the effects of changes in receptor binding and tracer transport changes on the perceived binding parameters obtained with the models. A constrained three-compartment kinetic model was demonstrated to be superior to other quantification models for the description of MeNTI kinetics and quantification of delta receptor binding in the human brain with 11C-labeled MeNTI.

Adult↗
PubMed1999

Bactericidal/permeability-increasing protein (rBPI21) in patients with hemorrhage due to trauma: results of a multicenter phase II clinical trial. rBPI21 Acute Hemorrhagic Trauma Study Group.

BACKGROUND: Infection and organ failure are the most common causes of death or serious complication in trauma patients surviving initial resuscitation and operation. Of the many possible causes of these complications, bacterial translocation and release of harmful cytokines and oxygen free radicals may play an important role in the pathogenesis of the complications associated with traumatic hemorrhage. Recombinant human bactericidal/permeability-increasing protein (rBPI21) has antibacterial and antiendotoxin properties, reduces cytokine levels, and increases survival in animal models of hemorrhagic shock. The primary objective of this study was to evaluate the safety and efficacy of prophylactic rBPI21 infusion in patients with hemorrhage due to trauma. METHODS: This was a phase II, multicenter, randomized, double-blind, placebo-controlled trial. Patients who required at least 2 U of blood were randomized to receive rBPI21 (4 mg x kg(-1) x d(-1) for 2 consecutive days) or an equivalent volume of placebo by continuous infusion within 12 hours of injury. The primary efficacy end point was mortality or serious complication occurring during the first 15 days of the study. Safety was monitored clinically and by laboratory panels during the study period. RESULTS: A total of 401 patients were treated (202 in the rBPI21 group and 199 in the placebo group). The composite end point rate of mortality or serious complication through day 15 was 46% in the placebo group and 39% in the rBPI21 group (hazard ratio = 0.79; p = 0.13). Secondary analysis, which adjusted for age, mechanism of injury, Injury Severity Score (1990 version), and units of blood received before study drug infusion showed similar results (hazard ratio = 0.79; p = 0.14). The proportion of patients who developed at least one serious organ dysfunction was 22% in the placebo group and 16% in the rBPI21 group (hazard ratio = 0.71; p = 0.14). The proportion of patients who developed either pneumonia or acute respiratory distress syndrome was 32% in the placebo group and 22% in the rBPI21 group (hazard ratio = 0.66; post hocp = 0.03). The beneficial trends of rBPI21 were observed in both blunt and penetrating trauma and were generally observed across different age groups, Injury Severity Scores, and units of blood transfused. No treatment difference was observed in mortality or resource utilization in this phase II study. CONCLUSION: rBPI21 was well-tolerated and demonstrated a favorable trend in reducing the composite primary end point of mortality or serious complication through day 15, especially respiratory complications, in patients with hemorrhage due to trauma. A phase III study is currently in progress.

Adolescent↗