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C Williams

Publications and source records attributed to C Williams.

At least 235 records · Page 13Linked to original sources
PubMed1997

Annexin V labels apoptotic neurons following hypoxia-ischemia.

The translocation of phosphatidylserine from the cytosol to the external surface of the plasma membrane has been documented as a characteristic feature of apoptosis in a number of cell types. Annexin V is a calcium-dependent phospholipid binding protein that has high affinity for phosphatidylserine. To investigate whether Annexin V provides a marker of apoptosis in the central nervous system we carried out histochemical analysis of its binding in the 21-day-old rat brain at various time-points following a moderate unilateral hypoxic-ischemic (HI) insult. The CA1 pyramidal neurons, which are selectively vulnerable to HI injury and that die by an apoptotic mechanism showed an increase in Annexin V binding 48-168 hours post-insult.

Animals↗
PubMed1997

Lack of activity of estradiol in rodent bone marrow micronucleus assays.

Estradiol has been evaluated in five independent rodent bone marrow micronucleus assays and has been found to be inactive. The dose-range evaluated extended from three daily doses of 20 micrograms/kg to the rat, a regimen that elicited a potent uterotrophic response from the animals, to single doses of between 10-150 mg/kg to the mouse. The mouse assays simulated and extended the conditions of test employed by earlier investigators who had found estradiol, and three structurally-related synthetic estrogens, to be active in mouse micronucleus assays over the dose range 1-10 mg/kg. It is concluded that estradiol is not genotoxic to the bone marrow of rodents. The top dose-level used in the present micronucleus assays (150 mg/kg) represented approximately 150,000 times the minimum estrogenic dose of this chemical to rodents, and that was considered to be above the dose at which useful genetic toxicity data would be generated for this potent estrogen. The maximum tolerated dose (MTD) of estradiol to rodents remains to be established.

Animals↗
PubMed1997

Tumor necrosis factor alpha-induced eosinophil accumulation in rat skin is dependent on alpha4 integrin/vascular cell adhesion molecule-1 adhesion pathways.

Tumor necrosis factor alpha (TNFalpha) is a cytokine implicated in the pathogenesis of numerous chronic and acute inflammatory conditions. In the present study, we have characterized the ability of TNFalpha in inducing eosinophil accumulation in rat skin and have shown the inhibitory effects of anti-alpha4 integrin and anti-vascular cell adhesion molecule-1 (VCAM-1) antibodies on this response. The intradermal injection of recombinant human TNFalpha induced a slowly developing, dose-dependent accumulation of 111In-eosinophils in rat skin that was maximal at the dose of 10(-11) mol/site. Coadministration of TNFalpha with the soluble TNFalpha receptor (p55)-IgG fusion protein (TNFR-IgG) totally inhibited the 111In-eosinophil accumulation induced by the cytokine. The TNFalpha-induced 111In-eosinophil accumulation was not affected after pretreatment of rats with the platelet-activating factor (PAF) receptor antagonist UK-74,505 or the antihuman interleukin-8 monoclonal antibody (MoAb) DM/C7. In contrast, the intravenous administration of an anti-alpha4 integrin MoAb, HP2/1 (3.5 mg/kg), or an anti-VCAM-1 MoAb, 5F10 (2 mg/kg), greatly inhibited the 111In-eosinophil accumulation induced by TNFalpha (the responses detected at 10(-11) mol/site were inhibited by 78% and 50%, respectively). These results show that TNFalpha is an effective inducer of eosinophil accumulation in vivo, with this response being dependent on an interaction between alpha4 integrins and VCAM-1.

Animals↗
PubMed1997

Human monoclonal antibodies to the V3 loop of HIV-1 with intra- and interclade cross-reactivity.

Five human anti-V3 mAbs were generated from Ab-producing cells derived from the blood of HIV-1-infected individuals from North America and selected using the V3 peptide of a divergent clade B isolate, HIV(RF). The anti-V3(RF) mAbs were mapped to a cluster of three overlapping epitopes present in the KSITKGP sequence located in the hypervariable region on the N-terminal side of the V3 loop. Broad immunochemical cross-reactivity was noted when the mAbs were tested for binding to V3 peptides derived from four clade A viruses, nine clade B viruses, and two clade C viruses. These results demonstrate antigenic relatedness in the V3 regions of these three HIV-1 clades. Affinities determined by surface plasmon resonance were higher for recombinant gp120 than for V3 peptides, suggesting that these mAbs recognize both linear and conformationally dependent epitopes of the V3 loop. Two of the mAbs neutralized four clade B T cell line-adapted and primary isolates with varying degrees of potency. The two neutralizing mAbs were the most cross-reactive with V3 peptides from several clades, had the highest affinity for V3(RF) and V3(MN), and stained HIV-infected cells. The data suggest that cross-reactivity, affinity, cell surface staining, and neutralizing activity are characteristics that describe an optimal fit between Ag and Ab. The results also demonstrate that the V3 peptides representing the sequence of several clade A, B, and C viruses share antigenic features that are recognized by the human immune response, a finding that suggests that cross-clade immunity to HIV-1 may be inducible by HIV-1 vaccines.

Antibodies, Monoclonal↗
PubMed1997

Prostaglandin H synthase-2 and cytosolic phospholipase A2 in the hypoxic-ischemic brain: role in neuronal death or survival?

The breakdown of membrane phospholipids and subsequent arachidonic acid metabolism to prostanoids is a well-documented brain response to cerebral ischemia. To further elucidate the components of this signal transduction pathway, immunocytochemistry was used to determine the levels of two potentially important enzymes, cytosolic phospholipase A2 (cPLA2) and prostaglandin H synthase-2 (PGHS-2), in the immature rat brain following moderate unilateral hypoxic-ischemia (HI). The CA1 pyramidal cells of the hippocampus which undergo delayed neuronal death on the injured side following HI demonstrated a significant induction of PGHS-2 immunoreactivity 48 h post-insult. However, a consistent increase in PGHS-2 was also evident in the resistant dentate granule cells at an earlier time point. Although PGHS-2 is present in both susceptible and resistant cell populations following HI, the possibility remains that divergence further down-stream in the pathway is responsible for selective vulnerability. In contrast to the neuronal PGHS-2 expression, cPLA2 immunoreactivity appears to be of glial origin with increases in and around the CAI-2 pyramidal cell layer at the 72-168-h time points. These results suggest that prostanoids are likely to serve important roles in HI brain damage and repair in infant brain.

Animals↗
PubMed1997

Insulin-like growth factor-I (IGF-I) immunoreactivity in the Alzheimer's disease temporal cortex and hippocampus.

IGF-I has been shown to enhance neuronal survival and inhibit apoptosis. IGF-I immunoreactivity was examined in the Alzheimer's disease and normal post-mortem human hippocampus and temporal cortex to determine whether IGF-I protein levels are altered in response to neurodegeneration. IGF-I immunoreactivity was induced in a subpopulation of GFAP-immunopositive astroglia in the Alzheimer's disease temporal cortex. These observations raise the possibility that IGF-I has a neuroprotective role in the Alzheimer's disease brain.

Aged↗
PubMed1997

Enhanced antitumor activity of combination radioimmunotherapy (131I-labeled monoclonal antibody A33) with chemotherapy (fluorouracil).

Monoclonal antibody (mAb) A33 reacts with an antigen expressed by >95% of colon cancer and normal colon epithelial cells. An earlier Phase I trial of 131I-labeled mAb A33 (131I-mAb A33) demonstrated bone marrow suppression as the dose-limiting toxicity, and although modest antitumor effects were seen, no normal colon toxicity was observed. In this study, a nude mouse model was used to test whether combinations of low-dose 131I-mAb A33 (0.1 mCi) and chemotherapy [5-fluorouracil (5-FU) or 5-FU + leucovorin, doxorubicin, or carmustine] enhance the antitumor effects, compared to 131I-mAb A33 alone or either drug regimen alone. 5-FU was administered either at 30 mg/kg/day for 5 days or at 75 mg/kg/day on days 1 and 5. In assessing the reduction in tumor volumes over the first 28 days of the experiment, 5-FU treatment (with or without leucovorin) in combination with 131I-mAb A33 showed a statistically significant additive antitumor effect compared to 131I-mAb A33 alone or to chemotherapy alone. When long-term survival was used as an end point, 38% of the mice treated with 5-FU and 131I-mAb A33 were disease free at 276 days compared to none from any other group, suggesting a synergistic effect. These data indicate that Phase II clinical trials combining radiolabeled antibody therapy with 5-FU-based treatments are warranted.

Animals↗
PubMed1997

Characteristics of participants in domestic violence. Assessment at the scene of domestic assault.

OBJECTIVE: To evaluate the characteristics of victims and perpetrators of domestic assault. DESIGN AND SETTING: Consecutive-sample survey study conducted at the scenes of police calls for domestic assault in Memphis, Tenn, in 1995. PARTICIPANTS: A total of 136 participants (72 victims and 64 assailants) involved in 62 incidents of domestic violence and 75 adult family members at the scene. MAIN OUTCOME MEASURES: Participants' responses to a confidential survey and review of police records. RESULTS: Of 62 episodes of domestic assault, 42 (68%) involved weapons and 11 (15%) resulted in serious injury. Fifty-five (89%) of 62 assault victims reported previous assaults by their current assailants, 19 (35%) of them on a daily basis. Although nearly all assault victims had called the police for help on previous occasions, only 12 (22%) reported having ever sought medical care, counseling, or shelter because of domestic assault. Sixty (92%) of the 64 assailants reportedly used alcohol or other drugs on the day of the assault. Of the assailants, 28 (44%) had a history of arrest for charges related to violence, and 46 (72%) had an arrest for substance abuse. Eleven (15%) of the victims were children. Children directly witnessed 53 (85%) of the assaults. CONCLUSIONS: Most victims of domestic violence who had called the police rarely used medical or mental health facilities for problems related to family violence despite frequent assaults. Victims and assailants were willing to discuss their histories of family violence and undergo assessments at the scenes of police calls.

Adolescent↗
PubMed1997

Bax expression in mammalian neurons undergoing apoptosis, and in Alzheimer's disease hippocampus.

Recent studies indicate that the proto-oncogene Bax, and other related proteins (eg Bcl-2) may play a major role in determining whether cells will undergo apoptosis under conditions which promote cell death. Increased expression of Bax has been found to promote apoptosis, while over-expression of Bcl-2 can inhibit apoptosis. To investigate the role of Bax in nerve cell death in the rat brain we examined the level of Bax expression in cells undergoing apoptosis, using a hypoxic-ischemic stroke model. We found that Bax was expressed at high levels in the nuclei of neurons in the hippocampus, cortex, cerebellum, and striatum on the control side, and that Bax levels increased in hippocampal neurons undergoing apoptosis on the stroke side, and then declined (correlating with cell loss). In the Alzheimer's disease hippocampi we found a concentrated localisation of Bax in senile plaques, which correlated with the localisation of beta-amyloid protein in adjacent sections from the same brains. beta-Amyloid positive plaques are thought to contribute to the Alzheimer's disease process, possibly via an apoptotic mechanism, and this may occur via an increase in Bax in these areas. Bax was also strongly stained in tau-positive tangles in Alzheimer's disease hippocampi, suggesting Bax may play a role in tangle formation. In addition, we observed a loss of Bax expression in the dentate granule cells of Alzheimer's disease hippocampi compared with moderate Bax expression in control hippocampi, and this loss may be related to the survival of these neurons in Alzheimer's disease. Finally, we observed substantially different staining patterns of Bax using three different commercially available antisera to Bax, indicating the need for caution when interpreting results in this area.

Adult↗
PubMed1997

Detection of mutations in multi-exon genes: comparison of conformation sensitive gel electrophoresis and sequencing strategies with respect to cost and time for finding mutations.

This report compares the relative advantages and disadvantages of two alternative strategies with respect to cost and time for finding mutations in the COL2A1 gene in patients with degenerative diseases of the joint. The coding region of the COL2A1 gene, 30 kb in length and containing 52 exons, can be analyzed using 26 genomic PCR products. The results indicate that the most efficient and cost effective way to screen large genes is a prescreen of the coding sequences followed by sequencing of a limited number of variant-PCR products.

Collagen↗
PubMed1997

Sumatriptan decreases food intake and increases plasma growth hormone in healthy women.

We studied the effect of the 5-HT1B/ID receptor agonist sumatriptan (6 mg s.c.) on plasma growth hormone and prolactin and food intake in 15 healthy female subjects using a double-blind, placebo-controlled, cross-over design. Sumatriptan significantly elevated plasma growth hormone but did not alter plasma prolactin. Sumatriptan also significantly lowered total food intake in a buffet meal, particularly decreasing the intake of fat. Our results indicate that 5-HT1B/ID receptors may be involved in the regulation of food intake in humans. In addition, while activation of 5-HT1B/ID receptors stimulates growth hormone release in both men and women, sumatriptan lowers plasma prolactin only in men, suggesting sex differences in the 5-HT regulation of prolactin release.

Adult↗
PubMed1997

5-HT2C receptor activation decreases appetite and body weight in obese subjects.

We studied the effect of 2 weeks administration of the 5-HT2C receptor agonist, m-chlorophenylpiperazine (mCPP), on appetite and body weight in 18 moderately obese subjects in a double-blind, placebo-controlled trial, mCPP caused a small but significant (0.75 kg) reduction in body weight and in subjective ratings of hunger. Plasma prolactin was significantly elevated by the final dose of mCPP. Our data suggest that during 2 weeks treatment in humans, mCPP may continue to activate brain 5-HT2C receptors, and that this effect is associated with decreases in appetite and body weight.

Adult↗
PubMed1997

Health after coronary stenting or balloon angioplasty: results from the Stent Restenosis Study.

This study was designed to compare health-related quality of life (HRQOL) in patients undergoing coronary stenting or balloon angioplasty in the randomized Stent Restenosis Study. The study sample was drawn from patients at nine U.S. clinical sites of the Stent Restenosis Study, a randomized trial comparing Palmaz-Schatz coronary stent implantation with conventional balloon angioplasty. One hundred ninety-nine consecutive patients were sent surveys 6 to 18 months after enrollment and 160 (80%) were returned. The survey sent to the patients included the Medical Outcomes Study 36-Item Short-Form Health Survey, the Canadian Cardiovascular Society Classification, and the Duke Activity Status Index. Although patients who underwent stenting had less angiographic restenosis and a tendency for fewer ischemic events, there were few differences in HRQOL after a mean of 456 days after randomization. The group that underwent stenting reported significantly less bodily pain than the group that underwent angioplasty (p = 0.02). Otherwise, there were no significant differences in generic or disease-specific measures. In a rating of their overall health, 47% of the group that underwent stenting and 45% of the group that underwent percutaneous transluminal coronary angioplasty reported very good or excellent health. In each group, 60% of the patients reported being symptom free from a cardiovascular perspective. This survey revealed no marked differences in long-term HRQOL between patients who underwent Palmaz-Schatz coronary stenting compared with those who underwent conventional angioplasty.

Aged↗
PubMed1997

Prescribed versus actual length of stay and inpatient neurorehabilitation outcome for brain dysfunctional patients.

OBJECTIVE: To determine (1) whether brain dysfunctional patients have better rehabilitation outcomes if they receive prescribed length of stay (LOS) versus less than prescribed and (2) if LOS and cognitive status relate to goal attainment. DESIGN: Prospective inception cohort study. STUDY SETTING: Medical center and a neurological institute. PARTICIPANTS: One hundred six patients with acute static brain lesions. MAIN OUTCOME MEASURES: Documentation of goal attainment at discharge and maintenance of goals 6 months after discharge. All subjects also received neuropsychological tests at admission and discharge. RESULTS: Patients who received prescribed LOS achieved their rehabilitation goals at discharge more frequently than patients who received less than prescribed LOS. There was, however, no difference between groups as to maintenance of rehabilitation goals 6 months after discharge. There was no relation between number of days spent in neurorehabilitation and number of goals achieved at discharge. Cognitive status at discharge was strongly related to achieving rehabilitation goals. CONCLUSION: Although LOS may not specifically relate to goal attainment in a heterogeneous group of brain dysfunctional patients, patients who receive the prescribed LOS and who show notable improvement in cognitive status tend to achieve rehabilitation goals, compared with patients who do not.

Adult↗
PubMed1997

Helicobacter pylori infection and chronic gastric acid hyposecretion.

BACKGROUND & AIMS: We have identified a subgroup of Helicobacter pylori-infected subjects with low or absent gastric acid output. The aim of this study was to document the morphological and functional abnormalities in these subjects and to assess the effect of eradicating the infection. METHODS: The 16 hypochlorhydric subjects (6 men) had a mean age of 55 years (range, 36-79 years). They underwent a 14C-urea breath test, H. pylori serology, fasting gastrin, gastric autoantibodies, gastroscopy with antral and body biopsies, and measurement of peak acid output to pentagastrin (PAO(PG)). Their histology was compared with that of age- and sex-matched duodenal ulcer and nonulcer dyspepsia patients (16 each). H. pylori infection was eradicated in the hypochlorhydric subjects, and the investigations were repeated 6 months later. RESULTS: Compared with controls, the hypochlorhydric subjects had less dense H. pylori colonization, body-predominant colonization and gastritis, and increased prevalence of body atrophy and intestinal metaplasia. Median PAO(PG) before eradication in the hypochlorhydric subjects was 1.1 mmol/h and increased to 12.6 mmol/h after eradication (P < 0.001), with no significant change in body atrophy or intestinal metaplasia. CONCLUSIONS: In some subjects, chronic H. pylori infection produces a body-predominant gastritis and profound suppression of gastric acid secretion that is partially reversible with eradication therapy.

Achlorhydria↗