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J S Smith

Publications and source records attributed to J S Smith.

At least 55 records · Page 3Linked to original sources
PubMed2001

Survey of bat populations from Mexico and Paraguay for rabies.

A mammalian survey was conducted in Mexico (October 1994-January 1996) and in Paraguay (August 1996-March 1997); a complete specimen was collected for each bat in the survey, including primary voucher specimen, ectoparasites, karyotype, and various frozen tissues. The surveys combined provided 937 brain samples (65 bat species) for rabies diagnosis. One male Lasiurus ega, collected in Paraguay, tested positive for the rabies virus (overall prevalence rate of 0.1%). Nucleotide sequence from a 300 bp region of the rabies nucleoprotein gene was compared with sequence obtained from representative rabies virus samples in the repository at the Centers for Disease Control and Prevention (Atlanta, Georgia, USA). Rabies virus extracted from the brain material of L. ega differed by only one nucleotide from a 300 bp consensus sequence (>99% homology) derived from samples for the variant of rabies virus transmitted by Lasiurus cinereus. Lasiurus ego differed by approximately 15% for the variant transmitted by Desmodus rotundus. Phylogenetic analysis found no evidence to suggest L. ego is a reservoir for rabies antigenic variant 6. The most likely explanation for rabies in L. ega was infection following contact with a rabid L. cinereus.

Animals↗
PubMed2001

Air-water partition constants for volatile methyl siloxanes.

Silicones are an important class of hydrophobic compounds in widespread use. To evaluate their fate in the environment, an accurate value of the air-water partition (Henry's law) constant is necessary, which, unfortunately, is lacking at present. A static head space and a newly developed dynamic vapor entry loop method were used to obtain the air-water partition constant for six volatile methyl siloxanes. Internally consistent data were obtained. The value of Henry's constant, as calculated from pure component vapor pressure and aqueous solubility, was 10- to 170-fold greater than the experimental values. A correction to the Henry's constant that involves the ratio of the thermodynamic activity coefficient for a methyl siloxane at infinite dilution to that at saturation solubility in the aqueous phase is proposed.

Environmental Pollutants↗
PubMed2000

Two general routes to 1,4-disubstituted-2,3,4,5-tetrahydro- 1H-3-benzazepines.

[structure] Two general routes to 1,4-disubstituted-2,3,4, 5-tetrahydro-1H-3-benzazepines are described. Both routes utilize an appropriately functionalized phenethylamino alcohol as the penultimate intermediate: the first route makes use of the reductive amination of a benzyl alkyl ketone with alpha-(aminomethyl)benzyl alcohol, while the second route utilizes the addition of a Grignard reagent to the oxazolidine derived from a substitued phenylacetaldehyde and alpha-(methylaminomethyl)benzyl alcohol. In all cases studied, the cis-1,4-disubstituted-2,3,4, 5-tetrahydro-1H-3-benzazepine was obtained as the major product.

Benzazepines↗
PubMed2000

Neurotrophic actions of a novel molluscan epidermal growth factor.

The mammalian epidermal growth factor (EGF) is expressed in the developing and adult CNS, and it has been implicated in the control of cell proliferation, differentiation, and neurotrophic events. Despite extensive evolutionary conservation of the EGF motif in a range of different types of proteins, secreted EGF homologs with neurotrophic actions have not been reported in invertebrates. In this study, we present a novel member of the family of EGF-like growth factors, an EGF homolog from the mollusc Lymnaea stagnalis (L-EGF), and we demonstrate that this protein has neurotrophic activity. Purified L-EGF is a 43-residue peptide and retains the typical structural characteristics of the EGF motif. The L-EGF cDNA reveals a unique precursor organization. In contrast to the multidomain mammalian EGFs, it consists of only two domains, a signal peptide and a single EGF motif. Conspicuously, the L-EGF precursor lacks a transmembrane domain, setting it apart from all other members of the EGF-family. L-EGF mRNA is expressed throughout embryonic development, in the juvenile CNS, but not in the normal adult CNS. However, expression in the adult CNS is upregulated after injury, suggesting a role of L-EGF in repair functions. This notion is supported by the observation that L-EGF evokes neurite outgrowth in specific adult Lymnaea neurons in vitro, which could be inhibited by an EGF receptor tyrosine kinase inhibitor. In conclusion, our findings further substantiate the notion that the EGF family has an early phylogenetic origin, and our data support a neurotrophic role for L-EGF during development and injury repair.

Amino Acid Sequence↗
PubMed2000

A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family.

The yeast Sir2 protein, required for transcriptional silencing, has an NAD(+)-dependent histone deacetylase (HDA) activity. Yeast extracts contain a NAD(+)-dependent HDA activity that is eliminated in a yeast strain from which SIR2 and its four homologs have been deleted. This HDA activity is also displayed by purified yeast Sir2p and homologous Archaeal, eubacterial, and human proteins, and depends completely on NAD(+) in all species tested. The yeast NPT1 gene, encoding an important NAD(+) synthesis enzyme, is required for rDNA and telomeric silencing and contributes to silencing of the HM loci. Null mutants in this gene have significantly reduced intracellular NAD(+) concentrations and have phenotypes similar to sir2 null mutants. Surprisingly, yeast from which all five SIR2 homologs have been deleted have relatively normal bulk histone acetylation levels. The evolutionary conservation of this regulated activity suggests that the Sir2 protein family represents a set of effector proteins in an evolutionarily conserved signal transduction pathway that monitors cellular energy and redox states.

DNA, Ribosomal↗
PubMed2000

Phosphorothioate substitution can substantially alter RNA conformation.

Phosphorothioate substitution-interference experiments, routinely used to stereospecifically identify phosphoryl oxygen sites that participate in RNA-ligand binding and RNA-directed catalysis, rest in their interpretation on the untested assumption that substitution does not alter the conformation of the modified molecule from its biologically active state. Using NMR spectroscopy, we have tested this assumption by determining the structural effect of stereospecific phosphorothioate substitution at five positions in an RNA hairpin containing the binding site for bacteriophage MS2 capsid protein. At most sites, substitution has little or no effect, causing minor perturbations in the phosphate backbone and increasing the stacking among nucleotides in the hairpin loop. At one site, however, phosphorothioate substitution causes an unpaired adenine necessary for formation of the capsid protein-RNA complex to loop out of the RNA helix into the major groove. These results indicate that phosphorothioate substitution can substantially alter the conformation of RNA at positions of irregular secondary structure, complicating the use of substitution-interference experiments to study RNA structure and function.

Adenine↗
PubMed2000

Investigation of germline PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 alterations in familial glioma.

Epidemiological studies suggest that some familial aggregations of glioma may be due to inherited predisposition. Many genes involved in familial cancers are frequently altered in the corresponding sporadic forms. We have investigated several genes known to be altered in sporadic gliomas for their potential contribution to familial glioma. Fifteen glioma patients with a family history of brain tumors were identified through the Mayo Clinic Department of Neurology (nine diffuse astrocytomas, two oligodendrogliomas, two mixed oligoastrocytomas, one pilocytic astrocytoma, and one pineal glioma). Eleven of the propositi had one or more first degree relative with a glioma. Lymphocyte DNA was derived from each of the patients and analyzed by polymerase chain reaction (PCR) and direct sequencing of the PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 genes. In addition, fluorescence in situ hybridization (FISH) was performed on EBV-transformed lymphocytes from each affected individual to detect germline copy number of the p16(INK4A)/p14(ARF) tumor suppressor region. A p53 germline point mutation was identified in one family with some findings of Li-Fraumeni syndrome, and a hemizygous germline deletion of the p16(INK4A)/p14(ARF) tumor suppressor region was demonstrated by FISH in a family with history of both astrocytoma and melanoma. Thus, whereas germ-line mutations of PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 are not common events in familial glioma, outside of familial cancer syndromes, point mutations of p53 and hemizygous deletions and other rearrangements of the p16(INK4A)/p14(ARF) tumor suppressor region may account for a subset of familial glioma cases. Collectively, these data lend genetic support to the heritable nature of some cases of glioma.

Adult↗
PubMed2000

A transcript map of the chromosome 19q-arm glioma tumor suppressor region.

Allelic loss of the chromosome 19q arm is a frequent event in human diffuse gliomas, suggesting that it contains a tumor suppressor gene. Recent deletion mapping studies have broadly implicated a 1.6-Mb interval between D19S241E and D19S596, with a limited subset of tumors, suggesting that the region may be as narrow as 150 kb. Focusing on this smaller interval, we have used cDNA selection, exon amplification, and genomic sequencing to identify three novel transcripts (EHD2, GLTSCR1, and GLTSCR2) and to map two known genes (SEPW1 and CRX). A partial transcript map of 19 transcripts and two EST markers has been constructed for the 1.6-Mb interval D19S241E-D19S596. Ten of these transcripts, including the 5 mapped to the 150-kb deletion interval, have been examined for alterations in a panel of gliomas with allelic loss of 19q. Tumor-specific alterations have not been identified in the transcripts examined thus far. Collectively, these data should facilitate subsequent efforts to identify and characterize the remaining transcripts in the 1.6-Mb interval.

Base Sequence↗
PubMed2000

Human papillomavirus infection and invasive cervical cancer in Paraguay.

HPV types 16 and 18 have been categorized as human carcinogens based on their strong associations with cervical cancer in previous case-control studies. Recent IARC studies in the Philippines, Thailand and Morocco show strong associations between invasive cervical cancer and less common HPV types, including HPV 31, 33, 45, 51, 52 and 58. We present results of a further IARC case-control study conducted in Asunción, Paraguay, to examine the association between specific HPV types and invasive cervical cancer as well as risk factors other than HPV. One-hundred thirteen incident histologically confirmed invasive cervical cancer cases and 91 age-matched hospital controls were recruited. A standardized questionnaire was administered to investigate known and suspected risk factors for cervical cancer. For HPV status determination, cervical biopsy specimens from case subjects and exfoliated cervical cells from control subjects were obtained. HPV DNA was ascertained using a GP5+/6+ PCR-based assay capable of detecting more than 33 HPV types. Overall HPV prevalence was 97% in the cervical cancer cases and 20% in the control subjects. As a single infection, HPV 16 was the predominant type with a prevalence of 48% among case subjects and 5.5% among control subjects. Significant associations with the risk of cervical cancer were detected as follows: any HPV type (OR = 114; 95% CI: 36-361); HPV 16 (OR = 910); HPV 18 (infinite OR); HPV 31 (OR = 110); HPV 33 (OR = 261); HPV 45 (OR = 129); and HPV 58 (OR = 36). In the multivariate model, risk factors other than HPV significantly associated with cervical cancer risk were a higher number of lifetime sexual partners, lower educational status and never having had a Pap smear. Strong associations were found between invasive cervical cancer and specific HPV types 16, 18, 31, 33, 45 and 58.

Adolescent↗
PubMed2000

EHD2, EHD3, and EHD4 encode novel members of a highly conserved family of EH domain-containing proteins.

Exon trapping from a bacterial artificial chromosome (BAC 78138) mapping to the 19q13.3 glioma tumor suppressor candidate region yielded two exons that recognized a 3.6-kb transcript on Northern blot. Screening of a human fetal brain cDNA library with these exons identified three novel genes, designated EHD2, EHD3, and EHD4, which are homologous to the recently characterized human EHD1 (testilin/HPAST) and its mouse homolog Ehd1, as well as to homologs in Drosophila (Past1) and Caenorhabditis elegans. Alignment of the predicted peptide sequences revealed striking similarities, with multiple conserved regions that include a nucleotide-binding consensus site at the N-terminus, a bipartite nuclear localization signal, and an eps15 homology (EH) protein-binding domain with an EF-hand motif at the C-terminus. The genes are specifically expressed, with EHD2 highly expressed in heart, EHD3 in brain and heart, and EHD4 in heart and pancreas. EHD2 was confirmed to originate from BAC 78138 at 19q13.3; radiation hybrid mapping localized EHD3 and EHD4 to 2p21 and 15q11.1, respectively; EHD1 has been previously mapped to 11q13. The three EHD1 paralogs therefore represent novel members of a family of human EH domain-containing proteins that may play a role in endocytosis and signaling. Mutation analysis of the five coding exons of EHD2 in gliomas failed to detect any tumor-specific alterations, thus indicating that EHD2 is an unlikely candidate for the 19q tumor suppressor gene.

Amino Acid Sequence↗
PubMed2000

Genetic alterations in adult diffuse glioma: occurrence, significance, and prognostic implications.

Our understanding of diffuse glioma development and progression has expanded remarkably over the past decade. As the genetic alterations responsible for these tumors are identified, molecular models of glioma pathogenesis are emerging and hold great promise to explain the biologic mechanisms of these neoplasms. Although these models continue to evolve and remain highly simplified, some of the genetic alterations that they encompass appear to be prognostically useful. Among the astrocytic gliomas, age and tumor grade are the most powerful indicators of patient survival, however, a wide range of variability remains, particularly among the low- grade and anaplastic astrocytomas. Recent reports indicate that alterations of the PTEN tumor suppressor gene are independent predictors of overall survival for anaplastic astrocytoma patients, helping to distinguish the cases with behavior resembling their more malignant counterparts, the glioblastomas. Among the oligodendroglial tumors, alterations of the 1p and 19q chromosome arms have emerged as potentially powerful predictors of overall patient survival and in vivo chemotherapeutic response, while alterations of the p16/CDKN2A tumor suppressor gene suggest shorter overall survival. As our molecular models continue to improve, through functional analyses and the identification of additional genetic contributors, we will expand our capacity to more effectively prognose these patients and to design rational therapeutic strategies.

Astrocytoma↗
PubMed2000

Mapping of the chromosome 19 q-arm glioma tumor suppressor gene using fluorescence in situ hybridization and novel microsatellite markers.

Allelic loss of chromosome arm 19q is a frequent event in human diffuse glioma, suggesting the presence of a tumor suppressor gene. Previous loss of heterozygosity (LOH) analyses have mapped this gene to a 1.4-megabase interval, between the genetic markers D19S412 and STD. Further narrowing of this interval has been limited by the resolution of mapped polymorphic markers. In the present study, we have used genomic clones mapped to 19q as fluorescence in situ hybridization (FISH) probes to map the breakpoints of 13 gliomas with 19q13.3 deletion boundaries. In addition, we have developed three new polymorphic microsatellite markers (D19S1180, D19S1181, and D19S1182) that map between D19S412 and STD and have used these new markers to identify two gliomas with small deletions between the D19S412 and STD markers. Collectively, these data suggest that the region of common deletion may be as narrow as 150 kb and should facilitate future efforts to identify the glioma 19q tumor suppressor gene.

Chromosome Deletion↗
PubMed2000

Kinetics of interaction of vanillin with amino acids and peptides in model systems.

Model systems were used to study the reaction kinetics of vanillin and pentalysine, lysine, glutathione, cysteine, aspartame, or phenylalanine (molar ratio 1:1) in phosphate buffer. The buffer pH was adjusted to the pK(a)(2) of the available alpha-amino group of each amino acid or peptide. Reductions of vanillin followed first-order kinetics at 55, 65, and 75 degrees C in the presence of each of the amino acids or peptides used. The reaction rates were accelerated as the temperature increased. The rate constants were highest for pentalysine followed by lysine, phenylalanine, glutathione/cysteine, and aspartame. The reduction of phenylalanine followed first-order kinetics, whereas the formation of its reaction product followed zero-order kinetics. The activation energy (E(a)) for the reaction ranged from 5.6 to 14.5 kcal/mol.

Amino Acids↗
PubMed2000

Amplification of the platelet-derived growth factor receptor-A (PDGFRA) gene occurs in oligodendrogliomas with grade IV anaplastic features.

Activation of the platelet-derived growth factor (PDGF) signaling system has been implicated in the development and malignant progression of diffuse gliomas. Overexpression of PDGF system components, particularly the alpha subtype receptor (PDGFRA), is common in glial tumors, and PDGFRA gene amplification has been reported in glioblastomas. In order to address the incidence of PDGFRA gene amplification in a broad set of diffuse gliomas, we used Southern and fluorescence in situ hybridization (FISH) analyses to examine 167 astrocytic gliomas (20 grade III and 147 grade IV), 41 anaplastic oligodendrogliomas, and 29 anaplastic oligoastrocytomas. PDGFRA gene amplification was identified in 4 anaplastic oligodendrogliomas and in a single case of anaplastic oligoastrocytoma, but in none of the malignant astrocytomas. Each of the 5 tumors with PDGFRA amplification displayed features generally associated with grade IV malignancy in astrocytic tumors. Consequently, our data indicate that this gene alteration is restricted to tumors having oligodendroglial differentiation and highly anaplastic features.

Blotting, Southern↗
PubMed2000

A robust structure-activity relationship (SAR) model for esters that cause skin irritation in humans.

A structure-activity relationship (SAR) model has been developed to discriminate skin irritant from nonirritant esters. The model is based on the physicochemical properties of 42 esters that were tested in humans for skin irritation. Nineteen physicochemical parameters that represent transport, electronic, and steric properties were calculated for each chemical. Best subsets regression analysis indicated candidate models for further analysis. Regression analyses identified significant models (p < 0.05) that had variables that were also significant (p < 0.05). These candidate models were evaluated using linear discriminant analysis to determine if the irritant esters could be discriminated from nonirritant esters. The stability of the model was evident from the consistency of parameters among ten submodels generated using multiple random sampling of the database. The sensitivity of the ten models, evaluated by "leave-one-out" cross-validation, ranged from 0. 846 to 0.923, with a mean of 0.885 +/- 0.025 (95% CI). The specificity ranged from 0.615 to 0.923, with a mean of 0.738 +/- 0.06 (CI). Compared with nonirritant esters, irritant esters had lower density, lower water solubility, lower sum of partial positive charges, higher Hansen hydrogen bonding parameter, and higher Hansen dispersion parameter. The results indicate that physicochemical features of esters contribute to their ability to cause skin irritation in humans, and that chemical partitioning into the epidermis and intermolecular reactions are likely important components of the response. This model is applicable for prediction of human irritation of esters yet untested.

Chemical Phenomena↗
PubMed2000

Age-related differences in the metabolic response to injury.

OBJECTIVE: To investigate the effect of age on the metabolic response to injury. METHODS: Fifty-two trauma patients meeting entrance criteria were prospectively enrolled. Patients were grouped by age: elderly, >60 years; and young, < or =60 years. After 4 days of nutrition support, physiologic and laboratory data were collected. Energy and nitrogen metabolism, and body composition were evaluated. RESULTS: Elderly patients demonstrated a reduced incidence of fever (48% vs. 77%,p = 0.027). Independent of body composition, temperature, and injury severity, oxygen consumption was 8% lower in the elderly (p = 0.0032). However, nitrogen loss and myofibrillar catabolic rate was not altered by age. Elderly subjects were more often hyperglycemic (38% vs. 0%, p < 0.0001) and azotemic (62% vs. 22%, p = 0.004), despite similar carbohydrate and protein intake. CONCLUSION: Fever is less common and oxygen consumption lower in elderly trauma patients. Postinjury myofibrillar protein catabolism and nitrogen loss are not influenced by aging. Metabolic complications of nutrition support (hyperglycemia, azotemia) are more common in elderly trauma patients.

Adult↗
PubMed2000

Outcome from injury: general health, work status, and satisfaction 12 months after trauma.

OBJECTIVE: We evaluated outcomes 12 months after trauma in terms of general health, satisfaction, and work status. METHODS: Two hundred forty-seven patients without severe neurotrauma were evaluated by interview during admission and by mailed self-report 6 and 12 months after trauma. Data were obtained from the Trauma Registry, interviews, and survey instruments. Baseline assessment was obtained with the Short Form 36 (SF36) and the Sickness Impact Profile (SIP) work scale. Outcome measures were the SF36, SIP work scale, Brief Symptom Inventory (BSI) depression scale, the Civilian Mississippi Scale for Posttraumatic Stress Disorder (PTSD), and a satisfaction questionnaire. Three regressions were determined for outcome. The dependent variables were general health and work status (linear) and satisfaction (logistic). Each regression controlled for baseline status and mental health, Injury Severity Score (ISS), and 12-month SF36 physical function before evaluating the effect of outcome mental health. RESULTS: Follow-up data were available for 75% of the patients at 6 months and 51% at 12 months. The mean age of patients was 37.2 +/- 0.9 years (+/-SEM), and 73% were male. Their average ISS was 13.9 +/- 0.6. Seventy percent of injuries were blunt force, 13.5 % were penetrating, and 16.5 % were burn injuries (mean total body surface area, 13.3 +/- 1.5%). Sixty-four percent of the patients had returned to work at 12 months. Follow-up SF36 mental health was associated with the dependent outcome in each regression. After controlling for baseline status and mental health, ISS, and outcome SF36 physical function, outcome mental health was associated with outcome SF36 general health (p < 0.001), SIP work status (p = 0.017), and satisfaction with recovery (p = 0.005). Outcome SF36 mental health was related to baseline mental health, 12-month PTSD and BSI depression scores, and increased drug and alcohol use. CONCLUSIONS: Twelve months after trauma, patients' work status, general health, and overall satisfaction with recovery are dependent on outcome mental health. This dependency persists despite measured baseline status, ISS, or physical recovery. The mental disease after trauma is attributable to poor mental health, the development of symptoms of PTSD and depression, and increased substance abuse. Trauma centers that fail to recognize, assess, and treat these injury-related mental health outcomes are not fully assisting their patients to return to optimal function.

Activities of Daily Living↗