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S Williams

Publications and source records attributed to S Williams.

At least 199 records · Page 11Linked to original sources
PubMed1999

Optical Contrast Variation Study of Nonaqueous Suspensions of Polymer Particles.

We analyze the core-shell structure of sterically stabilized hard sphere polymer colloids by optical contrast variation. Modified polymer particles are used which have the same refractive index as the suspending solvent. At low contrast, inhomogeneities in the core-shell structure of the particles become apparent. The particle form factor is shown to be a sensitive function of the temperature due to the interplay of scattering from the core and the stabilizing layer. We explore the dependence of particle form factors on composition, radius, and temperature and rationalize our observations in terms of a simple core-shell model. By exploiting the sensitivity of the form factors we are able to independently study the two components of a binary mixture of polymer particles. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Computerized histomorphometric assessment of protocol renal transplant biopsy specimens for surrogate markers of chronic rejection.

BACKGROUND: Chronic transplant rejection has emerged as the commonest cause of long-term renal allograft failure, and early identification of those grafts at risk could allow the targeting of specific therapies aimed at delaying this process. This study explores the usefulness of quantitative immunohistochemistry in defining biopsy-based surrogate markers of allograft damage. METHODS: A consecutive series of 52 renal transplant recipients immunosuppressed with cyclosporine were studied. Needle core transplant biopsies were performed at 1, 3, and 6 months postoperatively. Immunostaining for collagen III, and smooth muscle actin, tenascin, and infiltrating leukocytes was performed using an indirect immunoperoxidase technique. The interstitial area stained (%) was measured using a semiautomatic image analysis system. The results were related to glomerular filtration rates (GFR) measured at 6, 12, and 24 months after transplantation using rank correlation coefficients. RESULTS: The area fraction of immunostained collagen III correlated with 6-month GFR (r=-0.42, P=0.005) and was predictive of 12-month GFR (r=-0.32, P=0.03). An area fraction of immunostained collagen III of >40% at 6 months was associated with a significantly lower GFR at 24 months, compared with a percentage area of < or =40% (31+/-4 versus 45+/-4 ml/min/1.73 m2, P=0.01). Furthermore, a collagen III of >40% at 6 months identified patients who were at risk of progressive deterioration in graft function. CONCLUSIONS: Grafts with poorer long-term function can be predicted using 6-month protocol biopsy specimens immunostained for collagen III. This should prove to be a useful ad interim surrogate marker of allograft damage in studies addressing the effects of new immunosuppressive agents on the development of chronic rejection.

Adolescent↗
PubMed1999

Treatment of osteoporosis with MMP inhibitors.

In the current study, we examined the effects of minocycline on the osteopenia of ovariectomized (OVX) aged rats using the marrow ablation model. This injury induces rapid bone formation followed by bone resorption in the marrow cavity. Old female rats were randomly divided into five groups: sham, OVX, OVX + minocycline (5-15 mg/day, orally), OVX + 17 beta-estradiol (25 micrograms/day, subcutaneously), and OVX + both agents. Rats were OVX, treated with minocycline and/or estrogen, followed by marrow ablation. Bone samples were collected 16 days post-marrow ablation. X-ray radiography of bones operated on showed that treatment of OVX old rats with minocycline increased bone mass in diaphyseal region. Diaphyseal bone mineral density (BMD) was measured by DEXA scan. Diaphyseal BMD of OVX rats was increased 17-25% by treatment with 5-15 mg of minocycline or 17 beta-estradiol. The effects of minocycline and estrogen treatments on the expression of osteoblast and osteoclast markers were also examined. Northern and dot blot analysis of RNA samples showed that treatment of OVX aged rats with minocycline increased the expression of type I collagen (COL I) (49%) and decreased that of interleukin-6 (IL-6) (31%). In contrast, estrogen treatment decreased the expression of interleukin-6 (IL-6) (39%), carbonic anhydrase II (CA II) (36%), and osteopontin (OP) (37%). Neither minocycline nor 17 beta-estradiol had an effect on the expression of osteocalcin (OC) and alkaline phosphatase (AP). To elucidate the mechanism by which minocycline prevented the loss of bone in OVX aged rats, we examined the colony-formation potential of bone marrow stromal cells in ex vivo cultures. Minocycline stimulated the colony-forming efficiency of marrow stromal cells derived from old animals. We have therefore concluded that the modest increase in BMD noted in OVX aged rats, in response to minocycline treatment, may be due to a change in bone remodeling that favors bone formation; and the anabolic effect of minocycline is likely due to its effect on the expression of COL I and/or the metabolism of osteoprogenitor cells.

Absorptiometry, Photon↗
PubMed1999

Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP).

Activation of T lymphocytes to produce cytokines is regulated by the counterbalance of protein-tyrosine kinases and protein-tyrosine phosphatases, many of which have a high degree of substrate specificity because of physical association with their targets. Overexpression of hematopoietic protein-tyrosine phosphatase (HePTP) results in suppression of T lymphocyte activation as measured by T cell antigen receptor-induced activation of transcription factors binding to the 5' promoter of the interleukin-2 gene. Efforts to pinpoint the exact site of action and specificity of HePTP in the signaling cascade revealed that HePTP acts directly on the mitogen-activated protein (MAP) kinases Erk1 and 2 and consequently reduces the magnitude and duration of their catalytic activation in intact T cells. In contrast, HePTP had no effects on N-terminal c-Jun kinase or on events upstream of the MAP kinases. The specificity of HePTP correlated with its physical association through its noncatalytic N terminus with Erk and another MAP kinase, p38, but not Jnk or other proteins. We propose that HePTP plays a negative role in antigen receptor signaling by specifically regulating MAP kinases in the cytosol and at early time points of T cell activation before the activation-induced expression of nuclear dual-specific MAP kinase phosphatases.

Enzyme Activation↗
PubMed1999

Twins and maternal smoking: ordeals for the fetal origins hypothesis? A cohort study.

OBJECTIVE: To assess the direct and indirect effects of being a twin, maternal smoking, birth weight, and mother's height on blood pressure at ages 9 and 18 years. DESIGN: Longitudinal study. SUBJECTS: Cohort born in 1972-3. SETTING: Dunedin, New Zealand. MAIN OUTCOME MEASURE: Blood pressure at ages 9 and 18 years. RESULTS: Compared with singletons, twins had a systolic blood pressure 4.55 (95% confidence interval 1.57 to 7.52) mm Hg lower at age 9 after adjustment for direct and indirect effects of sex, maternal smoking, mother's height, socioeconomic status, and birth weight, as well as concurrent height and body mass index. Blood pressure in children whose mothers had smoked during pregnancy was 1.54 (0.46 to 2.62) mm Hg higher than in those whose mothers did not. The total effect of birth weight on systolic blood pressure at age 9 was -0.78 (-1.76 to 0.20) mm Hg and that for mother's height was 0.10 (0.06 to 0.14) mm Hg. Similar results were obtained for systolic blood pressure at age 18. The total effect of twins, maternal smoking, and birth weight on diastolic blood pressure was not significant at either age. CONCLUSIONS: Twins had lower birth weight and lower systolic blood pressure at ages 9 and 18 than singletons. This finding challenges the fetal origins hypothesis. The effect of maternal smoking was consistent with the fetal origin hypothesis in that the infants of smokers were smaller and had higher blood pressure at both ages. This may be explained by pharmacological rather than nutritional effects. The total effect of birth weight on systolic blood pressure, after its indirect effect working through concurrent measures of height and body mass index was taken into account, was small.

Adolescent↗
PubMed1999

The effect of race and sex on physicians' recommendations for cardiac catheterization.

BACKGROUND: Epidemiologic studies have reported differences in the use of cardiovascular procedures according to the race and sex of the patient. Whether the differences stem from differences in the recommendations of physicians remains uncertain. METHODS: We developed a computerized survey instrument to assess physicians' recommendations for managing chest pain. Actors portrayed patients with particular characteristics in scripted interviews about their symptoms. A total of 720 physicians at two national meetings of organizations of primary care physicians participated in the survey. Each physician viewed a recorded interview and was given other data about a hypothetical patient. He or she then made recommendations about that patient's care. We used multivariate logistic-regression analysis to assess the effects of the race and sex of the patients on treatment recommendations, while controlling for the physicians' assessment of the probability of coronary artery disease as well as for the age of the patient, the level of coronary risk, the type of chest pain, and the results of an exercise stress test. RESULTS: The physicians' mean (+/-SD) estimates of the probability of coronary artery disease were lower for women (probability, 64.1+/-19.3 percent, vs. 69.2+/-18.2 percent for men; P<0.001), younger patients (63.8+/-19.5 percent for patients who were 55 years old, vs. 69.5+/-17.9 percent for patients who were 70 years old; P<0.001), and patients with nonanginal pain (58.3+/-19.0 percent, vs. 64.4+/-18.3 percent for patients with possible angina and 77.1+/-14.0 percent for those with definite angina; P=0.001). Logistic-regression analysis indicated that women (odds ratio, 0.60; 95 percent confidence interval, 0.4 to 0.9; P=0.02) and blacks (odds ratio, 0.60; 95 percent confidence interval, 0.4 to 0.9; P=0.02) were less likely to be referred for cardiac catheterization than men and whites, respectively. Analysis of race-sex interactions showed that black women were significantly less likely to be referred for catheterization than white men (odds ratio, 0.4; 95 percent confidence interval, 0.2 to 0.7; P=0.004). CONCLUSIONS: Our findings suggest that the race and sex of a patient independently influence how physicians manage chest pain.

Age Factors↗
PubMed1999

Ulnar neuropathy as a complication of macular hole surgery.

OBJECTIVE: To report a series of patients manifesting ulnar neuropathy as an extraocular complication following macular hole surgery and facedown positioning. METHODS: Retrospective chart review of 7 patients identified by the operating surgeon as developing ulnar neuropathy during the immediate postoperative period after undergoing vitrectomy surgery with fluid-gas exchange for macular hole followed by at least 1 week of strict facedown positioning. RESULTS: All 7 patients developed symptoms of ulnar neuropathy, including paresthesias, dysesthesias, pain, weakness, and muscle atrophy. Signs included abnormal electromyogram, prolonged nerve conduction velocities, and impaired neurologic clinical test results in patients examined. Symptoms did not resolve with cessation of facedown positioning, and with follow-up ranging from 3 to 24 months all patients had persistent symptoms. All patients had positioned themselves with their arms continuously flexed. Three of 7 patients had placed pressure directly on their bent elbows. CONCLUSIONS: Ulnar neuropathy is an extraocular complication of macular hole surgery that can be attributed to arm position during postoperative facedown positioning. Surgeons performing macular hole surgery should caution their patients to minimize the amount of time spent with their elbows in a flexed position. Particular effort should be made to minimize pressure on the bent elbow.

Aged↗
PubMed1999

Changing infants' sleep position increases risk of sudden infant death syndrome. New Zealand Cot Death Study.

OBJECTIVE: To examine whether the prone sleeping position may increase the risk for sudden infant death syndrome (SIDS), particularly in infants unused to prone sleep. DESIGN: A 3-year (1987-1990) case-control study. SETTING: Nationwide study in New Zealand. SUBJECTS: Four hundred eighty-five infants who died of SIDS and 1800 controls. MAIN OUTCOME MEASURES: Infants were classified as unaccustomed to prone if their usual sleep position was nonprone and they were placed prone for the last sleep. Secondary prone was used to describe infants placed nonprone but found prone. RESULTS: Infants usually and last placed nonprone were at the lowest risk for SIDS (odds ratio [OR], 1.0); those usually and last placed prone were at increased risk (adjusted OR, 4.6; 95% confidence interval, 3.4-6.3). Risk was greatly increased among infants unaccustomed to the prone position (adjusted OR, 19.3; 95% confidence interval, 8.2-44.8). These infants accounted for 8% (31/ 386) of all SIDS deaths. Ninety percent (28/ 31) of infants in this group were found prone, and 71% (20/28) of those found prone were found with their faces turned down into bedding-a position in which asphyxia has been implicated as a mechanism of death. In addition, 138 infants who died of SIDS were last placed nonprone. Forty-seven infants (34%) in this group were found prone (secondary prone), and 60% (28/47) of those found prone were found with their faces turned down into the bedding. This group accounted for 12% of all SIDS deaths. Most of these infants (91% [43/47]) were usually placed nonprone. CONCLUSIONS: Infants placed supine to sleep were at the lowest risk of SIDS, which supports the recommendation that this is the preferred sleeping position for healthy infants. In New Zealand, 20% of SIDS deaths involved lack of experience with the prone sleeping position. Our findings suggest the possibility that an infant's competence in escaping from potentially lethal situations during prone sleep (eg, the face-down position) may be impaired by inexperience in prone sleeping. Great caution should be exercised in placing infants unaccustomed to the prone sleeping position in the prone position.

Case-Control Studies↗
PubMed1999

Dephosphorylation of ZAP-70 and inhibition of T cell activation by activated SHP1.

Studies with motheaten mice, which lack the SHP1 protein tyrosine phosphatase, indicate that this enzyme plays an important negative role in T cell antigen receptor (TCR) signaling. The physiological substrates for SHP1 in T lymphocytes, however, have remained unclear or controversial. To define these targets for SHP1 we have compared the effects of constitutively active and inactive mutants of SHP1 on TCR signaling. Expression of wild-type SHP1 had a very small effect on the TCR-induced tyrosine phosphorylation of ZAP-70 and Syk, even when SHP1 was overexpressed 20 - 100-fold over endogenous SHP1. Inactive SHP1-D421A and wild-type SHP2 were without effects. Constitutively active SHP1-DeltaSH2 had a more pronounced effect on ZAP-70 and Syk, even when expressed at near physiological levels. SHP1-DeltaSH2 also inhibited events downstream of ZAP-70 and Syk, such as activation of the mitogen-activated protein kinase Erk2 and the transcriptional activation of the interleukin-2 gene. In contrast, a constitutively active SHP2-DeltaSH2 had no statistically significant effect (although it caused a slight augmentation in some individual experiments). None of the constructs influenced the anti-CD3-induced tyrosine phosphorylation of the TCR zeta-chain or phospholipase Cgamma1, indicating that Src family kinase function was intact. Taken together, our findings support the notion that ZAP-70 and Syk can be direct substrates for SHP1 in intact cells. However, the two SH2 domains of SHP1 did not facilitate its recognition of ZAP-70 and Syk as substrates in intact cells. Therefore, we suggest that SHP1 is not actively recruited to inhibit TCR signaling induced by ligation of this receptor alone. Instead, we propose that ligation of a distinct inhibitory receptor leads to the recruitment of SHP1 via its SH2 domains, activation of SHP1 and subsequently inhibition of TCR signals if the inhibitory receptor is juxtaposed to the TCR.

Animals↗
PubMed1999

Characterization of TCR-induced receptor-proximal signaling events negatively regulated by the protein tyrosine phosphatase PEP.

The proline-, glutamic acid-, serine- and threonine-enriched protein tyrosine phosphatase PEP, which is expressed primarily in hematopoietic cells, was recently discovered to be physically associated with the 50-kDa cytosolic protein tyrosine kinase (PTK) Csk, an important suppressor of Src family PTK, including Lck and Fyn in T cells. We report that this phosphatase has an inhibitory effect on TCR-induced transcriptional activation of the c-fos proto-oncogene and elements from the IL-2 gene promoter. Catalytically inactive mutants of PEP had no effects in these assays. Expression of PEP also reduced activation of the N-terminal c-Jun kinase Jnk2 in response to receptor ligation, but not in response to UV light. In agreement with a more receptor-proximal site of action, we found that PEP reduced the TCR-induced increase in tyrosine phosphorylation of an Lck mutant, Lck-Y505F, which is only phosphorylated on tyrosine 394, the positive regulatory site. Finally, we observed that PEP reduced c-fos activation in a synergistic manner with Csk, supporting the notion that these two enzymes form a functional team acting on Src family kinases involved in TCR signaling.

Humans↗
PubMed1999

Estrogen promotes the initial migration and inception of NgCAM-dependent calcium-signaling by new neurons of the adult songbird brain.

The adult avian forebrain continues to generate neurons from ventricular zone (VZ) precursor cells, whose neuronal progeny then migrate into the brain parenchyma. Migrating neurons respond to the Ig-family adhesion molecule NgCAM with increments in cytosolic calcium, and migration is disrupted by anti-NgCAM Ig. The calcium response to NgCAM is developmentally restricted to bipolar migrants during a period spanning 6 to 9 DIV. This period corresponds to the postmitotic age at which new neurons leave the adult VZ to traverse a subjacent layer of estrogen-receptive "gatekeeper" neurons. Since neuronal passage through this layer occurs concurrently with the onset of NgCAM-dependent calcium signaling, we asked whether acquisition of the calcium response to NgCAM required estrogen exposure. Among neurons arising from explants of the adult finch neostriatal VZ, only those supplemented with estrogen developed calcium responses to NgCAM; neither explants raised in the absence of estrogen, nor those supplemented with testosterone, did so. Neurons in all three groups expressed NgCAM, had equivalent baseline calcium levels, and responded identically to K+-depolarization. Nonetheless, many more neurons migrated from explants of both finch and canary VZ raised in estrogen-supplemented media than from their estrogen-deprived counterparts, even though no effect of estrogen on neuronal survival per se was noted. These findings suggest that estrogen encourages the initial departure and assumption of signal competence by neurons arising from the adult avian VZ, thereby promoting their parenchymal recruitment and migration success.

Animals↗
PubMed1999

High-resolution mapping of discrete representational areas in rat somatosensory cortex using blood volume-dependent functional MRI.

The present study documents the use of an iron oxide-based blood-pool contrast agent in functional magnetic resonance imaging to monitor activity-related changes in cerebral blood volume (CBV) resulting from peripheral sensory stimulation and the application of this technique to generate high-resolution functional maps. Rats, anesthetized with alpha-chloralose, were imaged during electrical stimulation (3 ms, 3 Hz, 3 V) of forelimb or hindlimb. Activation maps were generated by cross-correlation of the measured signal response and a square-wave function representative of the stimulus for each image pixel. Multislice imaging produced functional maps consistent with the known functional anatomy of rat primary somatosensory (S-I) cortex. Imaging with improved temporal resolution demonstrated rapid (<6 s) CBV increases which were sustained and relatively stable (coefficient of variation = 0.17 +/- 0.02) for forelimb stimulation periods of up to 5 min. Enabled by this sustained response we generated high-resolution (approximately 100 micrometer in-plane) functional maps showing discrete forelimb and hindlimb activation. This technique offers many advantages over other methods for the study of brain activity in the rat and has resolution sufficient to be useful in reorganization studies.

Animals↗
PubMed1999

Attenuating tumor necrosis factor alpha does not ameliorate other cytokine and peroxidase products during sepsis.

BACKGROUND: Recent trials utilizing single anticytokine agents have shown no consistent survival benefit in improving the outcome of sepsis. Since an entire cascade of mediators contributes to the underlying pathophysiology, it is not surprising that monotherapy has proven unsuccessful. The purpose of this study was to measure the effects of attenuating tumor necrosis factor (TNF)alpha early in sepsis. METHODS: Three groups of Sprague-Dawley rats were studied. All animals were infused with live Escherichia coli, with group I and group II rats additionally receiving a matrix metalloproteinase inhibitor. Serum levels of TNFalpha, interleukin (IL)-6, malondialdehyde (MDA), and lipid hydroperoxide (LOOH) were compared. RESULTS: TNFalpha showed a significant decrease, yet IL-6, MDA, and LOOH (markers of sepsis) levels remained abnormally elevated. CONCLUSION: Despite significantly attenuating TNFalpha, the septic response continued. This supports the concept that in sepsis, monotherapy directed at attenuating a single cytokine cannot overcome the tissue-damaging effects of an entire cascade of mediators.

Animals↗
PubMed1999

In vitro abrasion using an air-powder polishing device and its quantification by radiotracer measurement.

OBJECTIVES: This study was conducted to examine the assessment of abrasion of two different materials after neutron activation. METHODS: A fissure sealant material (Fissurit F/VOCO with a compressive strength of 235 MPa) and a glass ionomer cement (Aqua Ionofil/VOCO with a compressive strength of 170 MPa) were activated by irradiation with neutrons. Subsequent measurements of the full-energy-peak (FEP) (1368.55 keV of 24Na) were made of the sample materials before and after abrasion via exposure to the air-powder polishing to accurately describe substance loss. RESULTS: Abrasion varied more than three-fold between the two materials. SIGNIFICANCE: Neutron activation and radiotracer measurement allows the quantification of abrasion effects in different materials. In comparison with other current methods its use may allow a superior measurement accuracy and precision in determining the abraded mass.

Air Abrasion, Dental↗
PubMed1999

Outcome for adjustment disorder with depressed mood: comparison with other mood disorders.

BACKGROUND: A review of the research literature on the diagnostic category of adjustment disorder indicates that its construct validity has not been established. Nevertheless, the diagnosis is made frequently, with an estimated incidence of 5-21% in psychiatric consultation services for adults. METHODS: Retrospective data was used to evaluate the construct validity of the adjustment disorder diagnostic category. The data primarily consisted of SF-36 Health Status Survey responses by a large group of adult psychiatric outpatients before treatment and again six months after beginning treatment. Subjects were divided into five diagnostic groups, and MANOVA, MANCOVA and chi square were used to clarify relationships among diagnoses, sociodemographic data and SF-36 scores. RESULTS: Diagnostic categories were significantly different at baseline, but did not differ in terms of outcome at six-months follow-up. There was a significant gender difference at baseline and a significant difference in gender distribution across diagnostic categories. LIMITATIONS: Structured interviews were not used for initial diagnoses, nor is there an estimate of the reliability of diagnoses among the clinicians. The patient attrition rate for six-months follow-up data was about 50%. Finally, patients received individualized treatment, with some patients receiving both medication and psychotherapy. CONCLUSIONS: Female patients were significantly more likely to be diagnosed with major depression or dysthymia than with an adjustment disorder. Females were also more likely than males to score lower on the mental health related scales of the SF-36 at admission. Patients diagnosed with an adjustment disorder scored higher on all SF-36 scales than did the other diagnostic groups at baseline and again at follow-up. There was no significant difference among diagnostic groups with regard to treatment outcome, suggesting that the adjustment disorder group can benefit as much as the other groups from treatment.

Adjustment Disorders↗