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K Williams

Publications and source records attributed to K Williams.

At least 127 records · Page 7Linked to original sources
PubMed1999

Association of Blood Clotting Factors I and VII with Phospholipid Monolayers at the Air-Water Interface.

Phospholipid monolayers adsorbed at the air-water interface are useful model membranes and have been employed to study the interactions between phospholipids and blood clotting factors I and VII. Factor I is a non-membrane-binding protein and was found to penetrate both distearoylphosphatidylcholine (DSPC) and dipalmitoylphosphatidylcholine (DPPC) monolayers at low lipid pressures. At high lipid pressures, the protein was crowded out of the interface. Factor I penetration of phospholipid monolayers was independent of hydrocarbon chain length, while penetration was maximized with electrolytes in the subphase. Factor VII is a membrane binding protein and was found to penetrate a DPPC monolayer only when electrolytes were added to the subphase. Factor VII penetrated DSPC monolayers regardless of electrolyte addition in the subphase, and its interactions with DSPC films are attributed to protein-lipid hydrophobic interactions. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Rapid rise in the incidence of type 2 diabetes from 1987 to 1996: results from the San Antonio Heart Study.

BACKGROUND: The prevalence of type 2 diabetes has increased in the early part of the 20th century, particularly in developing countries. There is now evidence that the prevalence also continues to increase in developed countries, including the United States. However, it is unknown whether this increase is due to a rise in the incidence of diabetes or to decreasing diabetic mortality or both. METHODS: Participants in the San Antonio Heart Study, who were nondiabetic at baseline and who returned for a 7- to 8-year follow-up examination, were examined for secular trends in the incidence of type 2 diabetes. Risk factors for diabetes, such as obesity, were also examined. Patients were enrolled in the San Antonio Heart Study from 1979 to 1988 and 7- to 8-year incidence of diabetes was determined from 1987 to 1996. RESULTS: A significant secular trend in the 7- to 8-year incidence of type 2 diabetes was observed in Mexican Americans (5.7% for participants enrolled in 1979 to 15.7% for participants enrolled in 1988). In non-Hispanic whites, the incidence increased from 2.6% for participants enrolled in 1980 to 9.4% for participants enrolled in 1988 (P = .07) . After adjusting for age and sex, the secular trend remained significant in Mexican Americans and borderline significant in non-Hispanic whites. This indicates that between 1987 and 1996 the 7- to 8-year incidence of type 2 diabetes approximately tripled in both ethnic groups. The overall secular trend also remained significant after adjusting for additional risk factors for diabetes, such as obesity. A rising secular trend in obesity was also observed. CONCLUSIONS: There has been a significant increasing secular trend in the incidence of type 2 diabetes in Mexican Americans and a borderline significant trend in non-Hispanic whites participating in the San Antonio Heart Study. Unlike other cardiovascular risk factors such as lipid levels, cigarette smoking, and blood pressure, which are either declining or under progressively better medical management and control, and unlike cardiovascular mortality, which is also declining, obesity and type 2 diabetes are exhibiting increasing trends. Thus, obesity and diabetes could easily become the preeminent US public health problem.

Adult↗
PubMed1999

Genetic pattern of prostate cancer progression.

Genetic alterations in primary prostate cancer (CaP) have been extensively studied, yet little is known about the genetic mechanisms underlying progression of primary CaP to metastatic prostate cancer. As a result, it is not possible to distinguish clinically indolent localized disease from potentially life-threatening tumors with high metastatic potential. To address this question, we collected tissue from 34 autopsy-derived metastases, samples rarely analyzed in previous studies. These were compared to a separate set of 17 prostatectomy specimens containing 22 foci of CaP associated with 49 examples of high-grade prostatic intraepithelial neoplasia (PIN), a histological precursor of CaP. We compared the loss of heterozygosity (LOH) profiles of high-grade PIN, primary CaP and metastases by analyzing 33 microsatellite markers previously found to have high frequencies of LOH in primary CaP. These markers were on chromosomes 5q, 6q, 7q, 8p, 9p, 10q, 11p, 13q, 16q, 17, 18q and 21q. In addition, markers on chromosomes 4p, 11q, 14q and 20q with no reported LOH in primary CaP were analyzed to determine the frequency of background LOH. In PIN lesions, the rate of LOH was significant only at D5S806 (20%) and D16S422 (29%). In addition, different PIN lesions within the same prostate gland were genetically diverse, indicating divergent evolution of synchronous neoplastic precursor lesions. LOH frequency was progressively higher in primary CaP and metastatic lesions. In primary CaP, significant losses occurred at the 8p, 10q, 11p, 16q, 17p, 18q and 21q loci (range 17-43%). Distinct patterns of LOH frequencies were observed in primary CaP compared with metastases. Although some loci (D16S422, D17S960, D21S156) showed similar frequencies of LOH in primary CaP and metastatic CaP, most other loci showed up to 7-fold metastasis-related increases. The metastatic samples revealed previously unrecognized prostate cancer LOH at D5S806, D6S262, D9S157, D13S133 and D13S227. These significant stage-specific differences in LOH frequency specify genetic loci that may play key roles in CaP progression and could represent clinically useful biomarkers for CaP aggressiveness.

Adenocarcinoma↗
PubMed1999

[Back pain].

Explore the source record for details and available documents.

Back Pain↗
PubMed1999

Stereoselective disposition of tiaprofenic acid enantiomers in rats.

The pharmacokinetics and metabolic chiral inversion of the S(+)- and R(-)-enantiomers of tiaprofenic acid (S-TIA, R-TIA) were assessed in vivo in rats, and in addition the biochemistry of inversion was investigated in vitro in rat liver homogenates. Drug enantiomer concentrations in plasma were investigated following administration of S-TIA and R-TIA (i.p. 3 and 9 mg/kg) over 24 hr. Plasma concentrations of TIA enantiomers were determined by stereospecific HPLC analysis. After administration of R-TIA it was found that 1) there was a time delay of peak S-TIA plasma concentrations, 2) S-TIA concentrations exceeded R-TIA concentrations from approximately 2 hr after dosing, 3) Cmax and AUC(0-infinity) for S-TIA were greater than for R-TIA following administration of S-TIA, and 4) inversion was bidirectional but favored inversion of R-TIA to S-TIA. Bidirectional inversion was also observed when TIA enantiomers were incubated with liver homogenates up to 24 hr. However, the rate of inversion favored transformation of the R-enantiomer to the S-enantiomer. In conclusion, stereoselective pharmacokinetics of R- and S-TIA were observed in rats and bidirectional inversion in rat liver homogenates has been demonstrated for the first time. Chiral inversion of TIA may involve metabolic routes different from those associated with inversion of other 2-arylpropionic acids such as ibuprofen.

Animals↗
PubMed1999

Perceived and physiological indicators of relaxation: as different as Mozart and Alice in chains.

The effects of listening to different types of music on perceived and physiological indicators of relaxation were evaluated. Fifty-six undergraduate students, 24 males and 32 females, mean age of 21, were randomly assigned to listen to classical, hard rock, self-selected relaxing music, or no music. Participants' relaxation level, skin temperature, muscle tension and heart rate were evaluated before and after exposure to a music condition. Analyses of variance using baseline measures as covariates indicated that skin temperature decreased for all conditions (p = 0.001) and the classical, self-selected relaxing music and no music groups reported significant increases in feelings of relaxation (p = 0.004). These results partially support the hypothesis that classical and self-selected relaxing music can increase perceptions of relaxation to a greater degree than listening to hard rock music. However, no differences were found between different types of music on physiological indicators of arousal. Implications for using music to reduce stress were discussed.

Adult↗
PubMed1999

HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages.

Infection of macrophage lineage cells is a feature of primate lentivirus replication, and several properties of primate lentiviruses seem to have evolved to promote the infection of macrophages. Here we demonstrate that the accessory gene product Nef induces the production of two CC-chemokines, macrophage inflammatory proteins 1alpha and 1beta, by HIV-1-infected macrophages. Adenovirus-mediated expression of Nef in primary macrophages was sufficient for chemokine induction. Supernatants from Nef-expressing macrophages induced both the chemotaxis and activation of resting T lymphocytes, permitting productive HIV-1 infection. These results indicate a role for Nef in lymphocyte recruitment and activation at sites of virus replication.

Adenoviridae↗
PubMed1999

Assessment of therapeutic response of oropharyngeal and esophageal candidiasis in AIDS with use of a new clinical scoring system: studies with D0870.

We developed and compared five scoring systems designed to quantitate therapeutic response in cases of oropharyngeal candidiasis. We utilized prospectively collected data on 114 patients treated with several doses of the azole D0870. Patients were infected with fluconazole-susceptible (n = 49) or -resistant organisms (MIC, > or = 16 mg/mL; n = 61). Patients with fluconazole resistance had lower CD4+ cell counts at baseline; more symptoms (P = .0006); a higher frequency of dysgeusia (P = .004), dysphagia (P = .006), and throat pain (P = .0034); and greater oral coverage by plaques of Candida. There was no difference between the two groups in terms of colony-forming units, and any change did not correlate with response to therapy. Resolution of dysphagia (P < .01) and oral pain (P < .01) correlated well with response to therapy, unlike retrosternal pain and throat pain, which were also less frequent. Xerostomia, a "furry" taste, and dysgeusia were frequent nonspecific symptoms. Scoring system C, weighting resolution of a symptom higher than absence of a symptom at baseline, yielded the best correlation with global outcome (r = 0.86) and allows the quantitation of incomplete but clinically beneficial responses to therapy.

AIDS-Related Opportunistic Infections↗
PubMed1999

Inefficient in vivo repair of mismatches at an oncogenic hotspot correlated with lack of binding by mismatch repair proteins and with phase of the cell cycle.

Repair rates of mismatched nucleotides located at an activating hotspot of mutation, H-ras codon 12, have been analyzed in vivo in mammalian cells. Repair rates at codon 12 are significantly improved in cells synchronized to the G(1) stage of the mammalian cell cycle as compared with non-synchronous cells, demonstrating that mismatch repair mechanisms are active in G(1). Repair rates in non-synchronous cells for the same mismatches at a nearby non-hotspot of mutation, H-ras codon 10, are also significantly improved over repair rates at codon 12 in non-synchronous cells, demonstrating that DNA mismatch repair rates can differ depending on the sequence context. These results suggest that inefficiencies in mismatch repair are responsible, at least in part, for the well documented hotspot of mutation at codon 12. Further experiments involving gel-shift analysis demonstrate a mismatch-specific binding factor for which the degree of binding correlates with in vivo repair rates for each mismatch tested at the codon 12 location. This binding factor appears to be the hMutSalpha heterodimer as identified by monoclonal antibody assay and inhibition of binding by ATP. Furthermore, a lack of binding is observed only for G:A mismatches at the codon 12 location. This lack of binding correlates with the low rate of repair observed in vivo for G:A mismatches at codon 12 versus the improved repair rates for G:A mismatches at codon 10. This may have biological relevance in that G:C-->T:A tranversions are a common mutation at this location in naturally occurring human tumors. These results suggest that there is lowered efficiency in the kinetics of mismatch repair at codon 12. Mismatches at this location are therefore more likely to be replicated before repair, thus resulting in a mutation.

3T3 Cells↗
PubMed1999

Skill levels of educational interpreters working in public schools.

The Educational Interpreter Performance Assessment, or EIPA, is an evaluation tool designed specifically for educational interpreters. An evaluation using the EIPA considers the child's grade level, the sign language or sign system that the interpreter is using as well as any other child-specific factors. Fifty-nine educational interpreters were evaluated using the EIPA. They had different backgrounds and training, and used different types of sign language or sign language or sign systems. The results show that not all of the educational interpreters were qualified to provide a child with an adequate interpretation of classroom discourse. Less than half of the educational interpreters assessed in this study performed at a level considered minimally acceptable. These data also show that sign vocabulary skills were significantly better than grammatical skills. Eighteen interpreters were evaluated twice in order to test-retest reliability, which showed that scores were not significantly different between the two evaluations. The picture that emerges from these data is that many deaf children receive an interpretation of classroom discourse that may distort and inadequately represent the information being communicated.

Journal Article↗
PubMed1999

A study of loss of heterozygosity at 70 loci in anaplastic astrocytoma and glioblastoma multiforme with implications for tumor evolution.

Cancers that arise from astrocytes in the adult CNS present as either anaplastic astrocytomas (AAs) or as more aggressive glioblastomas multiforme (GBMs). GBMs either form de novo or progress from AAs. We proposed to examine the molecular genetic relationship between these CNS tumors by conducting a genome-wide allelic imbalance analysis that included 70 loci on examples of AA and GBM. We found significant loss of heterozygosity (LOH) at 13 discrete chromosomal loci in both AAs and GBMs. Loss was significant in both AAs and GBMs at 9 of these loci. AAs show the highest rates of LOH at chromosomes 1p, 4q, 6p, 9p, 11p, 11q, 13q, 14q, 15p, 17p, 17q, and 19q. GBMs showed the greatest losses at 1p, 6q, 8p, 9p, 10p, 10q, 11p, 13q, 17p, 17q, 18p, 18q, and 19q. GBMs also demonstrated significant amplification at the epidermal growth factor receptor locus (7p12). These data suggest that there are three classes of loci involved in glioma evolution. First are loci that are likely involved in early events in the evolution of both AAs and GBMs. The second class consists of AA-specific loci, typified by higher LOH frequency than observed in GBMs (4q, 6p, 17p, 17q, 19q). The third class consists of GBM-specific loci (6q, 8p, 10, 18q). Damage at these loci may either lead to de novo GBMs or permit existing AAs to progress to GBMs. Glioma-related LOH profiles may have prognostic implications that could lead to better diagnosis and treatment of brain cancer patients.

Astrocytoma↗
PubMed1999

Evaluation of apomorphine HCl effects on reproductive endpoints: studies in male rats and dogs.

Apomorphine HCl is currently in phase III clinical trials for the treatment of erectile dysfunction. The potential for reproductive toxicity in males was assessed based on a 13-week rat study--a fertility study in male rats--and a 6-month study in dogs. The subcutaneous (s.c.) route was selected to simulate the sublingual route in humans. Dosages of apomorphine were 0.0 (vehicle), 0.8, 2, and 8 mg/kg/day in the 13-week study in rats (20/group), with 8 mg/kg/day used for only 9 weeks. In the fertility study, 24 males/group were cohabited with females, and doses were 0.0, 0.2, 0.8, and 2 mg/kg/day. Males were treated for 4 weeks prior to cohabitation and for 5 weeks throughout cohabitation. Organ weights, including testis and left epididymis, sperm count and morphology in the epididymis, and sperm motility in the vas deferens were evaluated. Male fertility index, and in females, the numbers of fetuses, implantation sites, and corpora lutea were counted. Male dogs (five/group) were dosed with 0.04, 0.1, or 0.4 mg/kg/day for 6 months. Epididymal and prostate weight, and testicular and epididymal histology were evaluated. Daily morbidity/mortality, weekly clinical observations, body weight, and food consumption were evaluated in all studies. No adverse effect was observed in any of the reproductive parameters in the studies. The NOEL for reproductive toxicity was approximately equal to 0.4 mg/kg/day in dogs and > or = 2 mg/kg/day in rats. These doses in rats and dogs correlated with plasma levels of approximately 240 and 130 ng/mL, and AUCs of 200 and 100 ng.h/mL, respectively. These levels suggest a safety margin for the evaluated male reproductive endpoints of at least 104 times based on the Cmax, and 44 times based on AUC of the clinical dose.

Animals↗
PubMed1999

Unstable dimension variability in coupled chaotic systems.

Systems of coupled chaotic maps and flows arise in many situations of physical and biological interest. The aim of this paper is to analyze and to present numerical evidence for a common type of nonhyperbolic behavior in these systems: unstable dimension variability. We show that unstable periodic orbits embedded in the dynamical invariant set of such a system can typically have different numbers of unstable directions. The consequence of this may be severe: the system cannot be modeled deterministically in the sense that no trajectory of the model can be realized by the natural chaotic system that the model is supposed to describe and quantify. We argue that unstable dimension variability can arise for small values of the coupling parameter. Severe modeling difficulties, nonetheless, occur only for reasonable coupling when the unstable dimension variability is appreciable. We speculate about the possible physical consequences in this case.

Journal Article↗
PubMed1999

A regulatory domain (R1-R2) in the amino terminus of the N-methyl-D-aspartate receptor: effects of spermine, protons, and ifenprodil, and structural similarity to bacterial leucine/isoleucine/valine binding protein.

There are complex interactions between spermine, protons, and ifenprodil at N-methyl-D-aspartate receptors. Spermine stimulation may involve relief of proton inhibition, whereas ifenprodil inhibition may involve an increase in proton inhibition. We studied mutations at acidic residues in the NR1 subunit using voltage-clamp recording of NR1/NR2B receptors expressed in Xenopus oocytes. Mutations at residues near the site of the exon-5 insert, including E181 and E185, reduced spermine stimulation and proton inhibition. Mutation NR1(D130N) reduced sensitivity to ifenprodil by more than 500-fold, but had little effect on sensitivity to spermine and pH. Mutations at six other residues in this region of the NR1 subunit reduced the potency and, in some cases, the maximum effect of ifenprodil. These mutants did not affect sensitivity to pH, glutamate, glycine, or other hallmark properties of N-methyl-D-aspartate channels such as Mg2+ block and Ba2+ permeability. Residues in this region presumably form part of the ifenprodil-binding site. To model this region of NR1 we compared the predicted secondary structure of NR1 (residues 19-400) with the known structures of 1,400 proteins. This region of NR1 is most similar to bacterial leucine/isoleucine/valine binding protein, a globular amino acid binding protein containing two lobes, similar to the downstream S1-S2 region of glutamate receptors. We propose that the tertiary structure of NR1(22-375) is similar to leucine/isoleucine/valine binding protein, containing two "regulatory" domains, which we term R1 and R2. This region, which contains the binding sites for spermine and ifenprodil, may influence the downstream S1 and S2 domains that constitute the glycine binding pocket.

Amino Acid Sequence↗
PubMed1999

Multiplex reverse transcriptase PCR assay for simultaneous detection of three fish viruses.

A multiplex reverse transcriptase (RT)-PCR assay was developed for the simultaneous detection of three different fish viruses: infectious pancreatic necrosis virus (IPNV), infectious hematopoietic necrosis virus (IHNV), and viral hemorrhagic septicemia virus (VHSV). The sensitivity levels of the multiplex RT-PCR assay were 100, 1, and 32 50% tissue culture infective doses/ml for IPNV, IHNV, and VHSV, respectively.

Animals↗