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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 343 records · Page 19Linked to original sources
PubMed1997

Peripheral blood progenitor cell mobilization using stem cell factor in combination with filgrastim in breast cancer patients.

The safety and optimal dose and schedule of stem cell factor (SCF) administered in combination with filgrastim for the mobilization of peripheral blood progenitor cells (PBPCs) was determined in 215 patients with high-risk breast cancer. Patients received either filgrastim alone (10 microg/kg/d for 7 days) or the combination of 10 microg/kg/d filgrastim and 5 to 30 microg/kg/d SCF for either 7, 10, or 13 days. SCF patients were premedicated with antiallergy prophylaxis. Leukapheresis was performed on the final 3 days of cytokine therapy and, after high-dose chemotherapy and infusion of PBPCs, patients received 10 microg/kg/d filgrastim until absolute neutrophil count recovery. The median number of CD34+ cells collected was greater for patients receiving the combination of filgrastim and SCF, at doses greater than 10 microg/kg/d, than for those receiving filgrastim alone (7.7 v 3.2 x 10(6)/kg, P < .05). There were significantly (P < .05) more CD34+ cells harvested for the 20 microg/kg/d SCF (median, 7.9 x 10(6)/kg) and 25 microg/kg/d SCF (median, 13.6 x 10(6)/kg) 7-day combination groups than for the filgrastim alone patients (median, 3.2 x 10(6)/kg). The duration of administration of SCF and filgrastim (7, 10, or 13 days) did not significantly affect CD34+ cell yield. Treatment groups mobilized with filgrastim alone or with the cytokine combination had similar hematopoietic engraftment and overall survival after PBPC infusion. In conclusion, the results of this study indicate that SCF therapy enhances CD34+ cell yield and is associated with manageable levels of toxicity when combined with filgrastim for PBPC mobilization. The combination of 20 microg/kg/d SCF and 10 microg/kg/d filgrastim with daily apheresis beginning on day 5 was selected as the optimal dose and schedule for the mobilization of PBPCs.

Adolescent↗
PubMed1997

Hepatic lipase deficiency increases plasma cholesterol but reduces susceptibility to atherosclerosis in apolipoprotein E-deficient mice.

The effect of hepatic lipase (HL) deficiency on the susceptibility to atherosclerosis was tested using mice with combined deficiencies in HL and apoE. Mice lacking both HL and apoE (hhee) have a plasma total cholesterol of 917 +/- 252 mg/dl (n = 24), which is 184% that of mice lacking only apoE (HHee; 497 +/- 161 mg/dl, n = 20, p < 0. 001). The increase in cholesterol was mainly in beta-migrating very low density lipoproteins, although high density lipoprotein cholesterol (HDLc) was also increased (53 +/- 37 versus 20 +/- 13 mg/dl, p < 0.01). Despite the increase in plasma cholesterol, we found that HL deficiency significantly decreased aortic plaque sizes in female mice fed normal chow (31 x 10(3) +/- 22 x 10(3) microm2 in hhee versus 115 x 10(3) +/- 69 x 10(3) microm2 in HHee, p < 0.001). Reduction of plaque sizes was also observed in female heterozygous apoE-deficient mice fed an atherogenic diet (2 x 10(3) +/- 2.5 x 10(3) microm2 in hhEe versus 56 x 10(3) +/- 49 x 10(3) microm2 in HHEe, p < 0.01). Changes in aortic lesion size were not apparent in the small number of male mice studied. In HHee females, both HDLc and the capacity of high density lipoprotein (HDL) particles to promote cholesterol efflux from cultured cells were 26% of the wild type. The absence of HL in hhee females partially restored HDLc levels to 57% and cholesterol efflux to 55% of the wild type. Circulating pre-beta1-migrating HDL were present in all mutants, suggesting that there are alternative pathways in the formation of these pre-beta-HDL not involving apoE, HL, or cholesteryl ester transfer protein. The improved capacity to promote cholesterol efflux, together with increased HDL, may explain why these animals can overcome the increase in atherogenic lipoproteins.

Animals↗
PubMed1997

Structural analysis of membrane-bound retrovirus capsid proteins.

We have developed a system for analysis of histidine-tagged (His-tagged) retrovirus core (Gag) proteins, assembled in vitro on lipid monolayers consisting of egg phosphatidylcholine (PC) plus the novel lipid DHGN. DHGN was shown to chelate nickel by atomic absorption spectrometry, and DHGN-containing monolayers specifically bound gold conjugates of His-tagged proteins. Using PC + DHGN monolayers, we examined membrane-bound arrays of an N-terminal His-tagged Moloney murine leukemia virus (M-MuLV) capsid (CA) protein, His-MoCA, and in vivo studies suggest that in vitro-derived His-MoCA arrays reflect some of the Gag protein interactions which occur in assembling virus particles. The His-MoCA proteins formed extensive two-dimensional (2D) protein crystals, with reflections out to 9.5 A resolution. The image-analyzed 2D projection of His-MoCA arrays revealed a distinct cage-like network. The asymmetry of the individual building blocks of the network led to the formation of two types of hexamer rings, surrounding protein-free cage holes. These results predict that Gag hexamers constitute a retrovirus core substructure, and that cage hole sizes define an exclusion limit for entry of retrovirus envelope proteins, or other plasma membrane proteins, into virus particles. We believe that the 2D crystallization method will permit the detailed analysis of retroviral Gag proteins and other His-tagged proteins.

Amino Acid Sequence↗
PubMed1997

Integrity of p53 in hepatitis B x antigen-positive and -negative hepatocellular carcinomas.

Inactivation of the tumor suppressor p53 seems to be important to the pathogenesis of hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus infection. Although this inactivation may be due to mutations in the p53 gene, recent evidence suggests that the hepatitis B virus-encoded X antigen (HBxAg) binds to and inactivates wild-type p53. Hence, experiments were designed to test the hypothesis that there is a low frequency of p53 mutations in HBxAg-positive HCC. HBxAg and p53 were assayed by immunohistochemistry (IHC) in HCC and nontumor liver from 16 Chinese patients, half of whom were hepatitis B surface antigen carriers. HBxAg was detectable in tumor and/or nontumor cells from all patients by IHC; six of these samples also had detectable p53. To determine whether p53 detection by IHC, and hence stabilization, is associated with mutation, sequencing of p53 exons 5-8 was performed with each patient sample. Wild-type sequences were found in 13 of 16 HBxAg-positive cases (81%). Hence, HBxAg is a common marker of HCC that correlates with the persistence of wild-type p53 among both carriers and noncarriers. The low frequency of p53 mutations in HCC in these patients implies that p53 inactivation may occur predominantly by complex formation with HBxAg.

Carcinoma, Hepatocellular↗
PubMed1997

Neuroleptic prescribing to the community elderly in Nottingham.

DESIGN: A cross-sectional pilot survey of computerized prescribing databases and written general practitioner records. Data were abstracted by the first author using a standard proforma. SETTING: Six out of 12 general practices situated in an area of north Nottingham known to have a high density of residential and nursing homes cooperated with the exercise (one was excluded because it lacked a computer system, one because the principal had a specialist commitment to old age psychiatry and four were self-excluded). PATIENTS: Patients recorded as receiving repeat prescriptions of oral preparations of thioridazine, chlorpromazine, promazine, haloperidol or trifluoperazine. MEASURES: Point prevalence rates of neuroleptic repeat prescribing classed by age group and, in the case of the elderly, residential status. For elderly recipients: median (range) duration on neuroleptics, median (range) time since last review and numbers (percentages) having various characteristics. RESULTS: Elderly patients were found to be more likely consumers of neuroleptic medication than their younger counterparts. If these results are extrapolated nationwide, then approximately half the patients receiving repeat prescriptions for the commonest oral neuroleptics emerge as elderly and of these about half are in nursing/residential care. Patients in nursing/residential homes suffering dementia formed the largest group of recipients, but have the least monitoring by psychiatric teams. CONCLUSION: The result highlight a need for a close partnership between primary care, community care facilities and old age psychiatric teams to ensure adequate monitoring and the implementation of psychological strategies to minimize their use.

Age Factors↗
PubMed1997

A clinical evaluation of risperidone in the treatment of schizophrenia: a 10-week, open-label, multicenter trial. ARCS Study Group. Assessment of Risperdal in a Clinical Setting.

The efficacy and safety of risperidone have previously been demonstrated in controlled clinical trials in hospitalized chronic schizophrenia patients who met strict research criteria. The present study was designed to evaluate the efficacy and safety of risperidone in a heterogeneous patient population. Patients were enrolled in the study if they had a diagnosis of schizophrenia (DSM-III-R) with or without acute exacerbation. Of the 945 patients from 158 psychiatric centers who entered this phase IV study, 558 completed the 10-week trial. During week 1, the dose of risperidone was titrated to 6 mg/day, maintained there for 1 week, and then adjusted over a 4-week period as clinically necessary; the dose was then fixed for the final 4-week period. The mean dose of risperidone at endpoint was 5.9 mg/day. Patients were evaluated at baseline and at weeks 2, 6, and 10, using Clinical Global Impression scale, Psychotic Symptoms Assessment scale, and Global Assessment of Functioning scale. Significant improvement in mean scores was found on each of these measures at endpoint. Comparable results were obtained at week 10 in treatment-resistant and non-treatment-resistant patients. Risperidone was generally well tolerated and the severity of extrapyramidal symptoms was significantly reduced at endpoint.

Adult↗
PubMed1997

Adaptation to the prismatic effects of refractive lenses.

Adaptation to the simple visual displacement of prisms was compared to that for refractive lenses, which have a varied prismatic effect. Subjects were made myopic using contact lenses, then corrected using spectacle lenses. The effect on the perceived direction of a randomly located target was assessed from pointing behavior. Prism adaptation showed a negative directional aftereffect but lacked intermanual transfer. Lens adaptation lacked a negative aftereffect but exhibited intermanual transfer. The results suggest that lens adaptation involves a recalibration of extraretinal eye movement information and multiple sets of lens adaptation can be retained for short periods.

Adaptation, Ocular↗
PubMed1997

Consequences of live poliovirus vaccine administration in chronic fatigue syndrome.

The effect of live oral polio virus vaccination on chronic fatigue syndrome (CFS) patients was examined in a double-blind study. CFS patients were allocated randomly to placebo (N = 7) or vaccine (N = 7) conditions. All controls subjects received the vaccine (9). Vaccine administration was not associated with clinical exacerbation of CFS. However, objective responses to the vaccine revealed differences between patients and controls: increased poliovirus isolation, earlier peak proliferative responses, lower T-cell subsets on certain days post vaccination and a trend for reduced gamma-interferon in the CFS-vaccine group. Polio vaccination was not found to be clinically contraindicated in CFS patients, however, there was evidence of altered immune reactivity and virus clearance.

Adult↗
PubMed1997

Effects of perceived listeners on speakers' vocal intensity.

The purpose of this study was to determine the amount of change in speakers' vocal intensity when a listener is located at various perceived versus actual physical distances from a speaker. Twelve men and 12 women with normal voices were asked to read a passage at three interspeaker distances in one of two conditions. In the perceived listener condition, participants were asked to "imagine" that the listener was located 3, 15, or 30 ft away. In the actual listener condition, one of the experimenters stood at each one of the three experimental distances. Conditions were counterbalanced. The results showed that men and women increased vocal intensity levels for all three interspeaker distances regardless of the type of condition. However, women showed larger increases than men at all interspeaker distances in both conditions. Data for both men and women combined showed that the amount of increase is < 6 dB, which indicates that speakers do not follow the inverse square law when raising vocal intensity. Clinical implications of the results are discussed.

Adult↗