Biomedical subjects

S Rodgers

Publications and source records attributed to S Rodgers.

51 records · Page 3Linked to original sources

PubMed1994

Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3.

The human DNA excision repair gene ERCC3 specifically corrects the nucleotide excision repair (NER) defect of xeroderma pigmentosum (XP) complementation group B. In addition to its function in NER, the ERCC3 DNA helicase was recently identified as one of the components of the human BTF2/TFIIH transcription factor complex, which is required for initiation of transcription of class II genes. To date, a single patient (XP11BE) has been assigned to this XP group B (XP-B), with ther remarkable conjunction of two autosomal recessive DNA repair deficiency disorders: XP and Cockayne syndrome (CS). The intriguing involvement of the ERCC3 protein in the vital process of transcription may provide an explanation for the rarity, severity, and wide spectrum of clinical features in this complementation group. Here we report the identification of two new XP-B patients: XPCS1BA and XPCS2BA (siblings), by microneedle injection of the cloned ERCC3 repair gene as well as by cell hybridization. Molecular analysis of the ERCC3 gene in both patients revealed a single base substitution causing a missense mutation in a region that is completely conserved in yeast, Drosophila, mouse, and human ERCC3. As in patient XP11BE, the expression of only one allele (paternal) is detected. The mutation causes a virtually complete inactivation of the NER function of the protein. Despite this severe NER defect, both patients display a late onset of neurologic impairment, mild cutaneous symptoms, and a striking absence of skin tumors even at an age of > 40 years. Analysis of the frequency of hprt- mutant T-lymphocytes in blood samples suggests a relatively low in vivo mutation frequency in these patients. Factors in addition to NER deficiency may be required for the development of cutaneous tumors.

Amino Acid Sequence↗

PubMed1992

Treatment of malignant melanoma and renal cell carcinoma with recombinant human interleukin-2: analysis of cytokine levels in sera and culture supernatants.

In this study we evaluated the clinical response of 12 patients with malignant melanoma and renal cell carcinoma (RCC) following administration of recombinant human interleukin-2 (rhIL-2) by continuous infusion. Serum samples taken before, during and following sequential courses of IL-2 were assayed for the presence of tumour necrosis factor alpha (TNF-alpha) IL-1 alpha, IL-6 and interferon gamma (IFN-gamma) and the presence or changes in these cytokines were examined with respect to clinical response data: our results did not show any direct correlation between the parameters measured and clinical outcome. In addition, peripheral blood mononuclear cells (PBMC) derived from 3 RCC patients were cultured in a serum-free environment and the resulting supernatants assayed for the production of these cytokines and compared to the corresponding serum levels. During one or more courses of treatment only 1 patient, who had metastatic bone disease, demonstrated detectable serum TNF-alpha; serum IL-6 levels were elevated in a proportion of all patients studied and a sustained IL-6 response occurred in a patient who had complete disease remission; IL-1 alpha was detected in the serum of 3 RCC patients; IFN-gamma could not be detected in any serum sample tested. Cytokine levels in sera and supernatants derived from 3 RCC patients were compared but no correlation was found: TNF-alpha and IL-6 were shown to be present at much higher concentrations in supernatants when compared to sera whereas the levels of IL-1 alpha were almost undetectable. This lack of correlation is probably due to the presence of "interfering" proteins in sera which either depress or enhance the ability to detect cytokines in sera using enzyme immunoassays.

Carcinoma, Renal Cell↗

PubMed1991

Malignant melanoma and renal cell carcinoma: immunological and haematological effects of recombinant human interleukin-2.

The immunological and haematological effects of continuous infusion of recombinant human interleukin-2 (rhIL-2) in 6 patients with metastatic melanoma and 6 with disseminated renal cell carcinoma are reported. In patients with malignant melanoma dacarbazine was given before IL-2; in renal cell carcinoma IL-2 alone was given. In malignant melanoma, 1 complete (CR) and 1 partial response (PR) were seen; 2 patients had stable disease (SD) and 2 progressive disease (PD). In renal cell carcinoma 4 patients had SD and 2 PD. Toxicity of IL-2 therapy was minimal. All patients showed increased cytotoxicity, that was not major histocompatibility complex restricted, towards target cells sensitive and insensitive to natural killer cells. These activities varied between individual patients and were less marked in cases of renal cell carcinoma. Cellular proliferative responses increased in all patients, being consistently higher following the first course of therapy, as did HLA-DR, CD16 and CD25 activation marker expression. Hypersegmentation of neutrophils and eosinophilia were commonly observed, and in renal cell carcinoma these changes were accompanied by abnormal lymphocyte morphology.

Aged↗

PubMed1991

Peptide accretions in the endoplasmic reticulum of magnocellular neurosecretory neurons in normal and experimentally manipulated rats.

Light microscopic observations using Nomarski interference contrast optics or darkfield optics on unstained aldehyde-fixed vibratome sections of hypothalami from normal young adult male and female Long Evans rats and from vasopressin-deficient Brattleboro rats, revealed the presence of cells in the supraoptic, paraventricular and periventricular nuclei which possessed yellow birefringent inclusions of globular or filamentous appearance in their somata. These inclusions were morphologically distinct from the large lipid droplets present in vasopressinergic magnocellular neurons of diabetes insipidus mice. Small portions of the vibratome sections containing the birefringent cells were excised and prepared for correlative electron microscopy. This revealed that the birefringent inclusions represented electron-dense material within cisterns of endoplasmic reticulum in magnocellular neurons. Antibodies to oxytocin or oxytocin-associated neurophysin immunolabelled the intracisternal electron-dense material and neurosecretory granules in resin-embedded ultrathin sections. Antibodies to vasopressin or vasopressin-associated neurophysin, and a panel of lectins did not label the intracisternal material. Quantitation revealed a small increase in the numbers of birefringent cells in aged rats and in rats drinking saline for 3 days. Subcutaneous injection of oestradiol benzoate for 7 days prior to fixation caused a large increase. After cessation of oestradiol administration the numbers of birefringent cells decreased; observations on the remaining cells showed that the endoplasmic reticulum cisterns were frequently fused with the plasmalemma, resulting in direct release of neurosecretory material into the extracellular spaces.

Animals↗

PubMed1987

Dipyridamole: pharmacokinetics and effects on aspects of platelet function in man.

1. The effect of dipyridamole on platelet function was measured in twelve normal subjects given 150 or 200 mg tablets as single and multiple doses, and in six subjects given single doses of 25, 50 and 100 mg and multiple doses of 50 mg 8 hourly. 2. Platelet aggregation was measured in response to ADP and collagen. In the subjects given 150/200 mg, the platelets were assayed for content of cyclic AMP and for formation of thromboxane after addition of collagen. The responses to ADP and collagen and the cyclic AMP content were assessed in both the presence and absence of added PGE1. The pharmacokinetics of dipyridamole were studied in all subjects. 3. One hour after 150/200 mg single doses of dipyridamole there was significant inhibition of platelet aggregation in response to both collagen and ADP. There was no detectable effect on aggregation at other time points or with lower doses of dipyridamole. The addition of PGE1 to platelets prior to testing did not enhance the effect of dipyridamole on platelet aggregation. 4. In multiple doses, dipyridamole (150/200 mg twice daily for 11 days) had no detectable effect on platelet aggregation. 5. Dipyridamole did not have any effect on platelet cyclic AMP content, whether or not PGE1 was added prior to assay. 6. Dipyridamole did not affect platelet thromboxane formation. 7. Plasma dipyridamole concentrations were maximal 1-2 h after ingestion, at the same time that inhibition of platelet aggregation was detected. The concentrations declined in a biexponential fashion, with a terminal half life of 24.1 +/- 1.9 h (mean +/- s.e. mean). In six of the 17 subjects, the mean steady state plasma concentration was less than 75% of the value predicted from the single dose data.

Adolescent↗

PubMed1986

Effect of pharmacist intervention on control of resistant hypertension.

The effect of a pharmacist's clinical intervention on blood pressure control in ambulatory adults with resistant hypertension was studied. Twenty patients of an internal medicine clinic who had diastolic blood pressures greater than 96 mm Hg on two consecutive visits and antihypertensive regimens consisting of two or more agents were entered in the study between November 1, 1980, and February 1, 1981. After asking each patient 15 questions about hypertension and its treatment, the pharmacist counseled the patient about antihypertensive therapy, obtained a medication history, and discussed diet. The patient's blood pressure was measured, and the pharmacist evaluated the appropriateness of the patient's antihypertensive regimen (based on compliance, adverse reactions, and regimen complexity) and possible reasons for the poor response to treatment. The pharmacist then recommended drug therapy to the physician; stepped care including hydrochlorothiazide, reserpine, and hydralazine was used when possible. Patients' mean age was 56 years. Most did not know the names of their medications or understand their dosage schedules. Eight patients had severe hypertension (193/124 +/- 23/4 mm Hg), five had moderate hypertension (161/109 +/- 20/2 mm Hg), and seven had mild hypertension (171/100 +/- 29/0 mm Hg). Factors contributing to poor blood pressure control were noncompliance and adverse drug effects. After five to eight months of follow-up, mean blood pressures for patients with severe, moderate, and mild hypertension were, respectively, 140/92 +/- 23/10 mm Hg, 131/92 +/- 8/6 mm Hg, and 137/88 +/- 26/3 mm Hg; the mean for each group was significantly different from baseline. In this study, pharmacists intervened successfully with patients and physicians to enhance blood pressure control through drug therapy.

Antihypertensive Agents↗

PubMed1978

Chemoresponses of Chlamydomonas reinhardtii.

Cells of Chlamydomonas reinhardtii have been found to respond to chemicals in two ways: chemokinesis and chemotaxis. Several amino acids, fatty acids, and inorganic salts can stimulate these responses.

Amino Acids↗

PubMed1977

Jaw wiring in treatment of obesity.

17 patients with severe (median percentage above ideal weight 100%) and resistant obesity underwent jaw wiring. There were no major complications and patients tolerated the procedure and subsequent minor inconveniences. All patients lost weight at a rate (median 25-3 kg in six months) comparable with that of intestinal bypass surgery and one achieved and maintained her ideal weight. Two-thirds of the patients, however, regained some weight after the wires were removed. Jaw wiring is a simple effective procedure which can be carried out in most hospitals, and has a place in an integrated approach to obesity.

Adolescent↗

PubMedDate not supplied

The reporting of crime and violence in the Los Angeles Times: is there a public health perspective?

The authors examine how crime and violence is reported and framed by the Los Angeles Times. Using a public health perspective, we examine whether health-oriented variables, such as causal factors and societal effects of crimes, are present in crime news stories. The classic stereotyping of crime and violence framing is strongly present in the Times. We discuss what changes would be useful to provide news consumers with a more accurate picture of crime in their community.

Bibliometrics↗

PubMedDate not supplied