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Biomedical subjects

R Palmer

Publications and source records attributed to R Palmer.

At least 91 records · Page 5Linked to original sources
PubMed1995

A comparative structural study on the steroids [1,2,5]oxadiazolo[3', 4':3,4]-5 alpha-pregn-16-en-20-one oxime (HS998), [1,2,5]oxadiazolo[3, 4':3,4]-5 beta-pregn-16-en-20-one (HS973) by NMR, molecular modeling, and X-ray investigations.

The molecular structure of the steroids [1,2,5]oxadiazolo[3', 4':3,4]-5 alpha-pregn-16-en-20-one oxime, [1,2,5]oxadiazolo[3',4':3, 4':3,4]-5 alpha-pregn-16-en-20-one and [1,2,5]oxadiazole]3',4':3,4]-5 beta-pregn-16-en-20-one has been determined. The proton-proton distances in the solid state from previous crystallographic studies are compared with the corresponding distances from novel and previous solution NMR as well as from novel in vacuo modeling studies.

Crystallization↗
PubMed1995

Down regulation of the octamer binding protein Oct-1 during growth arrest and differentiation of a neuronal cell line.

The octamer binding transcription/DNA replication factor Oct-1 is present in virtually all cell types including proliferating cell lines of neuronal origin but is not detectable in mature non-dividing neurons. Cell cycle arrest in G0/G1 and morphological differentiation of a neuronal cell line is accompanied by a decline in the level of Oct-1 DNA binding, although the level of DNA binding by another octamer binding protein, Oct-2 is unaltered. This effect is paralled by a decline in the level of the Oct-1 mRNA in the non-dividing cells. The decrease in Oct-1 levels occurs only with the production of a mature, non-dividing neuronal phenotype and not when the cells are arrested in late G1 and do not undergo morphological differentiation. The potential role of Oct-1 and other octamer binding proteins in gene regulation in neuronal cells and in their differentiation is discussed.

Animals↗
PubMed1995

Dual chamber pacing: how many patients remain in DDD mode over the long term?

OBJECTIVE: DDD pacing is better than VVI pacing in complete heart block and sick sinus syndrome but is more expensive and demanding. In addition, some patients have to be programmed out of DDD mode and this may have an important impact on the cost-effectiveness of DDD pacing. The purpose of this study was to determine how many patients remain in DDD mode over the long term (up to 10 years). DESIGN: A retrospective analysis of the outcome over 10 years of consecutive patients who had their pacemakers programmed initially in DDD mode. SETTING: A district general hospital. PATIENTS: 249 patients with DDD pacemakers. Sixty two patients (24.9%) had predominantly sick sinus syndrome and 180 (72.3%) had predominantly atrioventricular conduction disease. Mean (range) complete follow up for this group of patients was 32 months (1-10 years). RESULTS: Cumulative survival of DDD mode was 83.5% at 60 months. Atrial fibrillation was the commonest reason for abandonment of DDD pacing. Atrial fibrillation developed in 30 patients (12%), with atrial flutter in three (1.2%). Loss of atrial sensing or pacing, pacemaker mediated tachycardia, and various other reasons accounted for reprogramming out of DDD mode in eight patients (3.2%). Overall, an atrial pacing mode was maintained in 91% and VVI pacing was needed in only 9%. CONCLUSIONS: With careful use of programming facilities and appropriate secondary intervention, most patients with dual chamber pacemakers can be maintained successfully in DDD or an alternative atrial pacing mode until elective replacement, although atrial arrhythmia remains a significant problem. There are no good reasons, other than cost, for not using dual chamber pacing routinely as suggested by recent guidelines and this policy can be achieved successfully in a district general hospital pacing centre.

Aged↗
PubMed1995

Growth hormone and longitudinal bone growth in vivo: short-term effect of a growth hormone antiserum.

The control of longitudinal growth is poorly understood but GH is considered to be one of the major hormones regulating postnatal growth. However, there is dispute as to whether it has a direct or indirect action. To study the role of GH we used a polyclonal antiserum to rat GH and investigated changes in cell proliferation and enzyme activities associated with bone formation and resorption during longitudinal growth. IGF-I levels were measured by two independent RIAs, DNA synthesis by bromodeoxyuridine incorporation followed by immunocytochemistry and enzyme activities were quantified in situ by microdensitometry. After 1 day the percentage of chondrocytes undergoing DNA synthesis within the proliferative zone was reduced but no other parameters were affected. By day 4 the labelling index was the same as in pair-fed animals but the number of chondrocytes synthesising DNA was reduced as was the total width of the growth plate and that of the proliferative zone. Alkaline phosphatase (associated with mineralisation) was unchanged but glucose 6-phosphate dehydrogenase activity (associated with cell proliferation) was decreased. Osteoclastic tartrate-resistant acid phosphatase activity (associated with bone resorption) was also significantly reduced. Similar changes were apparent after 10 days. At no time was the circulating level of IGF-I decreased. These data suggest that, during longitudinal growth, GH affects the number of proliferating chondrocytes but not the percentage of cells undergoing DNA synthesis, indicating that its primary role may be on the commitment of prechondrocytes to a proliferative state. Furthermore, while GH does not seem to have any effect on skeletal mineralisation it may stimulate osteoclastic resorption of the primary spongiosa.

Acid Phosphatase↗
PubMed1994

Crystal structure of RNase T1 with 3'-guanylic acid and guanosine.

A modified method for the synthesis and separation of endo and exo guanosine 2',3'-cyclophosphorothioate (cGPS) has been developed. The exo diastereoisomer has been co-crystallized with RNase T1. cGPS is known to be a RNase T1 inhibitor but is also a very slow substrate. It was hydrolyzed during the crystallization, leaving 3'-guanylic acid (3'-GMP) in the active site. As a guanosine was also found to be bound in a subsite, the enzyme contains the products of the reaction of guanylyl-3',5'-guanosine. The structure was refined to a resolution of 1.7 A and yielded a final R value of 14.5%. In contrast to previous 3'-GMP complexes of RNase T1, the ribose phosphate moiety of the inhibitor is in contact with all the active site residues. The phosphate forms hydrogen bonds with Asn36, Tyr38, Arg77, His92, and with Asn49 from a symmetry-related molecule. The ribose 2'-OH is hydrogen-bonded to both Glu58 and His40. The interactions in the active site of the present structure are compared to those found in the 2'-GMP complex of RNase T1.

Binding Sites↗
PubMed1994

The structures of RNase A complexed with 3'-CMP and d(CpA): active site conformation and conserved water molecules.

The interactions of RNase A with cytidine 3'-monophosphate (3'-CMP) and deoxycytidyl-3',5'-deoxyadenosine (d(CpA)) were analyzed by X-ray crystallography. The 3'-CMP complex and the native structure were determined from trigonal crystals, and the d(CpA) complex from monoclinic crystals. The differences between the overall structures are concentrated in loop regions and are relatively small. The protein-inhibitor contacts are interpreted in terms of the catalytic mechanism. The general base His 12 interacts with the 2' oxygen, as does the electrostatic catalyst Lys 41. The general acid His 119 has 2 conformations (A and B) in the native structure and is found in, respectively, the A and the B conformation in the d(CpA) and the 3'-CMP complex. From the present structures and from a comparison with RNase T1, we propose that His 119 is active in the A conformation. The structure of the d(CpA) complex permits a detailed analysis of the downstream binding site, which includes His 119 and Asn 71. The comparison of the present RNase A structures with an inhibitor complex of RNase T1 shows that there are important similarities in the active sites of these 2 enzymes, despite the absence of any sequence homology. The water molecules were analyzed in order to identify conserved water sites. Seventeen water sites were found to be conserved in RNase A structures from 5 different space groups. It is proposed that 7 of those water molecules play a role in the binding of the N-terminal helix to the rest of the protein and in the stabilization of the active site.

Binding Sites↗
PubMed1994

Opinions on the traumatizing effects of child sexual abuse: evidence for consensus.

The aim of the study was to investigate peoples' views of characteristics associated with child sexual abuse (CSA) and place them in order of severity for subsequent trauma. Clinically relevant characteristics of CSA were presented in the form of a questionnaire to a sample of professionals working with CSA, a sample of student nonprofessionals and a sample of patients with eating disorders including a high proportion of CSA victims. A significant consensus existed across the three samples in the ranked order of characteristics from most to least severe for perceived adverse long-term outcome. Respondent sex, social class, or past sexual abuse experience had no significant effect on this concordance. The findings of this study have shown that professional, nonprofessional, and psychiatric patients opinions on CSA severity are consistent and coincide with clinical observations and empirical evidence. It is argued that a shared consensus on traumatic effects of CSA characteristics is important for the therapeutic process and may prove useful as a guideline for the assessment of severity in CSA cases.

Adolescent↗
PubMed1994

Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2.

Saethre-Chotzen syndrome is a common autosomal dominant form of craniosynostosis, which results in the premature fusion of cranial sutures. Craniosynostosis is commonly associated with abnormalities of 7p; Vortkamp et al. (Nature 352, 539-540) demonstrated that the GLI3 gene in 7p13 was disrupted in, patients with Greig syndrome and, more recently, the linkage of genetic markers from 7p with the Saethre-Chotzen syndrome locus has been reported (2,3). Here we report the analysis by fluorescence in situ hybridization of four patients with Saethre-Chotzen syndrome associated with apparently balanced translocations involving band 7p21.2 and different reciprocal chromosomes. We show that in all four patients the breakpoints in 7p are situated within a 6 cM region flanked by the genetic markers D7S488 and D7S493. These results provide further evidence that the genetic locus for Saethre-Chotzen syndrome is located in distal 7p.

Acrocephalosyndactylia↗
PubMed1994

Longitudinal bone mineral density changes in early rheumatoid arthritis.

A prospective longitudinal study of patients with early RA was performed to examine the influence of disease duration, disease activity and physical activity on bone loss. Sixty-seven patients with non-steroid treated RA of less than 5 yr duration, including 16 patients with disease duration less than 6 months, had BMD measurements of the femoral neck and the lumbar spine over a 12-month period using dual energy X-ray absorptiometry. The BMD changes were compared with values from 72 control patients and were also correlated with serial measurements of disease activity (measured by the Stoke Index) and disability [measured by the Health Assessment Questionnaire (HAQ) score], at 3-monthly intervals over the 12-month period. No significant differences in BMD changes were found between RA patients and controls overall. Patients with disease duration of less than 6 months had significantly greater loss of BMD at the femoral neck (-3.9%, S.E.M. 1.5) than the remainder of the cohort (-0.2%, S.E.M. 0.7) (P = 0.02) and controls (-0.8%, S.E.M. 0.6). Lumbar spine BMD changes correlated with the initial Stoke Index (Rs-0.373, P = 0.01) but not mean Stoke Indices. There was no correlation of BMD changes with age or HAQ scores. These findings suggest that significant bone loss occurs within the first few months of disease in patients with RA.

Adult↗
PubMed1994

Bone mineral density in nonsteroid treated early rheumatoid arthritis.

OBJECTIVES: To determine whether significant reduction in bone mass is detectable in early disease in patients with rheumatoid arthritis (RA) and to examine the possible influences of disease activity and physical disability on bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN). METHODS: LS and FN BMD values were measured and Z scores determined in a cross-sectional study of 104 patients with RA of less than five years duration. BMD values were also compared between a subgroup of 64 patients and a normal control group matched for age, sex, menopausal status and body mass. BMD values and Z scores were correlated with disease activity, measured by the Stoke Index, disability, measured by HAQ score, and disease duration. RESULTS: Premenopausal female patients with RA had significantly reduced mean FN Z scores (-0.62, 95% CI -0.30 to -0.94) which correlated with HAQ scores (Rs 0.358, p = 0.05) and age (Rs 0.397, p = 0.03). There were no significant changes of BMD in males or postmenopausal females. Disease duration and disease activity did not correlate with BMD changes. CONCLUSION: BMD is reduced in premenopausal female patients with early RA possibly related to the attainment of peak bone mass. No significant reduction of BMD was found in males or postmenopausal females with early disease. Physical disability but not disease activity appears to play a role in the reduction of FN bone mass.

Adult↗
PubMed1994

Efficacy and safety of granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in the prevention of nausea and vomiting induced by high-dose cisplatin.

PURPOSE: To assess the antiemetic effects and safety profile of four different doses of granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) when administered as a single intravenous (IV) dose for prophylaxis of cisplatin-induced nausea and vomiting. PATIENTS AND METHODS: One hundred eighty-four chemotherapy-naive patients receiving high-dose cisplatin (81 to 120 mg/m2) were randomized to receive one of four granisetron doses (5, 10, 20, or 40 micrograms/kg) administered before chemotherapy. Patients were observed on an inpatient basis for 18 to 24 hours, and vital signs, nausea, vomiting, retching, and appetite were assessed. Safety analyses included incidence of adverse experiences and laboratory parameter changes. RESULTS: After granisetron doses of 5, 10, 20, and 40 micrograms/kg, a major response (< or = two vomiting or retching episodes, and no antiemetic rescue) was recorded in 23%, 57%, 58%, and 60% of patients, respectively, and a complete response (no vomiting or retching, and no antiemetic rescue) in 18%, 41%, 40%, and 47% of patients, respectively. There was a statistically longer time to first episode of nausea (P = .0015) and vomiting (P = .0001), and fewer patients were administered additional antiemetic medication in the 10-micrograms/kg dosing groups than in the 5-micrograms/kg dosing group. As granisetron dose increased, appetite return increased (P = .040). Headache was the most frequently reported adverse event (20%). CONCLUSION: A single 10-, 20-, or 40-micrograms/kg dose of granisetron was effective in controlling vomiting in 57% to 60% of patients who received cisplatin at doses greater than 81 mg/m2 and totally prevented vomiting in 40% to 47% of patients. There were no statistically significant differences in efficacy between the 10-micrograms/kg dose and the 20- and 40-micrograms/kg doses. Granisetron was well tolerated at all doses.

Adolescent↗
PubMed1994

Development of the ability to make IgG and IgA in newborns and infants.

An understanding of the ontogeny of the human immune system may provide clues for methods to stimulate the immune response of neonates and young infants at an earlier age than is now possible. Knowledge of normal changes in immune response over time is necessary to evaluate infants for immunodeficiency.

Antibody Specificity↗
PubMed1994

Interleukin-11 expression in donor bone marrow cells improves hematological reconstitution in lethally irradiated recipient mice.

Lethally irradiated mice were transplanted with syngeneic bone marrow cells infected with a recombinant retrovirus vector containing the human interleukin-11 (hIL-11) cDNA under the control of the human cytomegalovirus (CMV) immediate early promoter. The hIL-11 RNA transcript from the vector was detected in the spleen and bone marrow of the recipient mice, and hIL-11 protein accumulated in their serum. The hematological reconstitution of these mice was compared with recipient mice rescued with bone marrow infected with the parental retrovirus vector not containing the hIL-11 cDNA. The hIL-11-expressing mice had an accelerated recovery of circulating platelets and red and white blood cells. Three months after the transplantation, bone marrow was harvested from the mice and used to rescue other lethally irradiated recipients. The hIL-11 mRNA and protein were also detected in these secondary recipients, and the mice showed improved hematological reconstitution relative to a control group. No abnormal cell proliferation or other histopathology was observed in the hIL-11-expressing mice.

Animals↗
PubMed1993

Activation of adrenal medullary L-arginine: nitric oxide pathway by stimuli which induce the release of catecholamines.

The activation of the L-arginine: nitric oxide (NO) pathway in the cat adrenal medulla by different stimuli which induce the release of catecholamines was studied. Stimuli that evoke catecholamine release, such as electrical stimulation of splanchnic nerves (50 V, 5 Hz, 1 ms), methacholine (100 microM), dimethyl-4-phenylpiperazinium iodide (DMPP; 10 microM), high K+ (35 mM) and alamethicin (15 micrograms ml-1) also caused a rise in cyclic GMP in the perfused cat adrenal medulla. NG-nitro-L-arginine methyl ester (L-NAME; 1 mM) abolished the rise in cyclic GMP induced by these stimuli without affecting the catecholamine release. Bovine adrenal medulla cytosol contained an NO synthase which was L-arginine- and Ca(2+)-dependent. In conclusion cat and bovine adrenal medulla stimulated with a variety of secretagogues synthesize NO from L-arginine to activate the soluble guanylate cyclase. The present data do not rule out a role for cyclic GMP in the regulation of catecholamine secretion; however, it seems more plausible that cyclic GMP may play a role in controlling local blood flow and thus the access of the released catecholamines to the systemic circulation during stressful conflicts.

Adrenal Medulla↗
PubMed1993

Meiotic crossing-over in nondisjoined chromosomes of children with trisomy 21 and a congenital heart defect.

We have used DNA polymorphisms to study meiotic crossovers of chromosome 21q in 27 nuclear families. Each family had a child with Down syndrome and a congenital heart defect. Twenty DNA polymorphisms on chromosome 21 were used to determine parental and meiotic origin of nondisjunction and to identify crossovers. Twenty-four cases were of maternal origin, and three were of paternal origin. Twenty-two unequivocal crossover events were identified. Sixteen crossovers were observed in 22 chromosome pairs nondisjoining at the second meiotic division. Fifty percent of crossover events in MI nondisjunction are detectable by molecular genetic means. Thus, the results suggest that, in this sample, each nondisjoined chromosome 21 pair has been involved in at least one crossover event.

Adolescent↗