PubMed Health⌕ Search

Biomedical subjects

D Parry

Publications and source records attributed to D Parry.

At least 55 records · Page 3Linked to original sources
PubMed1994

Absence of cyclin D/cdk complexes in cells lacking functional retinoblastoma protein.

Cyclins D1, D2 and D3 are thought to function in the G1 phase of the cell division cycle by regulating the activity of cyclin-dependent protein kinases. All three D-type cyclins can be shown to associate with two specific kinases, cdk4 and cdk6, providing at least six possible combinations. To establish whether different cell types require different subsets of these complexes and whether they are altered in tumours where D-cyclin expression is perturbed, we surveyed a series of tumour cell lines and compared them where possible to non-tumorigenic counterparts. Although complexes involving cdk4 or cdk6 were readily observed in many of the cell lines, no complexes were detectable in human cells harbouring DNA tumour virus oncoproteins or in which the retinblastoma gene product (pRb) is mutated or missing. These data suggest that as well as being a potential substrate for D-cyclin-kinases, functional pRb contributes to the formation or stability of the complexes, at least in human cells.

Breast Neoplasms↗
PubMed1994

CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1.

Deregulated expression of cyclin D1 is a feature of several neoplastic and proliferative disorders, but its normal role in the cell cycle remains unclear. Here we show that in a squamous carcinoma cell line with 11-fold amplification of the CCND1 gene, cyclin D1 associates specifically with p33cdk4 (PSK-J3) and p38cdk6 (PLSTIRE), two closely related members of the cyclin-dependent kinase (CDK) family. In these tumour cells, there is little evidence for an association between cyclin D1 and other CDKs, but in diploid human fibroblasts both CDK2 and CDK5 can be co-precipitated with cyclin D1, as well as CDK4. The data suggest that D-type cyclins participate in multiple interactions with CDKs but that the nature or stoichiometry of these associations may differ in different types of cell.

Amino Acid Sequence↗
PubMed1993

Iron chelation as a chemotherapeutic strategy for falciparum malaria.

To examine the effect of iron chelation against human malaria, 37 Zambians with asymptomatic Plasmodium falciparum infections were randomly assigned to 72-hr infusions of desferrioxamine B or placebo. Mean concentrations of ring forms decreased significantly with desferrioxamine B (P < 0.001) but not with a placebo. Over seven days of observation, mean parasite concentrations remained at the initial levels in six individuals originally given placebo, but decreased promptly with administration of desferrioxamine B (P = 0.001). Mean parasitemia was significantly lower for up to four weeks in 16 subjects treated with desferrioxamine B when compared with the eight who had received placebo only (P = 0.027). We conclude that iron chelation has antiplasmodial activity and may offer a new therapeutic strategy for falciparum malaria.

Adult↗
PubMed1992

Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria.

BACKGROUND: Cerebral malaria is a severe complication of Plasmodium falciparum infection in children, with a mortality rate of 15 to 50 percent despite antimalarial therapy. METHODS: To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria. To be enrolled, patients had to be less than six years old, have P. falciparum parasitemia, have normal cerebrospinal fluid without evidence of bacterial infection, and be in a coma from which they could not be aroused. Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine-pyrimethamine. The time to the recovery of full consciousness, time to parasite clearance, and mortality were examined with Cox proportional-hazards regression analysis. RESULTS: The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo (95 percent confidence interval, 0.7 to 2.3); the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group (P = 0.38). Among 50 patients with deep coma, the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine (95 percent confidence interval, 1.1 to 4.7), decreasing the median recovery time from 68.2 to 24.1 hours (P = 0.03). Among 69 patients for whom data on parasite clearance were available, the rate of clearance with deferoxamine was 2.0 times that with placebo (95 percent confidence interval, 1.2 to 3.6). Among all 83 patients, mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group (P = 0.52). CONCLUSIONS: Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria.

Child, Preschool↗
PubMed1992

Iron chelation with desferrioxamine B in adults with asymptomatic Plasmodium falciparum parasitemia.

To determine if iron chelation therapy has activity against human malaria, we administered desferrioxamine B in amounts of 100 mg/kg per day by continuous 72-hour subcutaneous infusions to 28 volunteers with asymptomatic Plasmodium falciparum infection in a randomized, double-blind, placebo-controlled crossover trial. Peripheral blood concentrations of P falciparum ring forms were determined at 12-hour intervals in all subjects and serum concentrations of desferrioxamine B + ferrioxamine (the iron complex of desferrioxamine B) were measured in 26 subjects. Geometric mean concentrations of asexual intraerythrocytic parasites decreased with both chelator and placebo treatment, but the decrement with desferrioxamine B was significantly greater than that with placebo (P less than .006) during both the initial and crossover periods. Compared with placebo, desferrioxamine B treatment was associated with an almost 10-fold enhancement of the rate of parasite clearance during both phases of the trial (P less than .007). Mean +/- SEM steady state concentrations of desferrioxamine B + ferrioxamine were 6.90 +/- 0.60 mumol/L at 36 hours and 7.72 +/- 0.68 mumol/L at 72 hours; in vitro, the ID50 has been reported to be approximately 4 to 20 mumol/L. No drug toxicity was detected. Parasitemia recurred in 19 of 24 participants followed-up over 1 to 6 months. We conclude that desferrioxamine B enhances the clearance of P falciparum parasitemia and that iron chelation may provide a new strategy to be developed for the treatment of malaria.

Adolescent↗
PubMed1992

Actinomycosis associated with pilonidal sinus of the penis.

We report a case of actinomycosis associated with a penile pilonidal sinus. This association does not appear to have been described previously. We recommend the submission of biopsies of unusual lumps in the genital region (fresh biopsies for bacteriological examination and fixed biopsies for histomorphological assessment).

Actinomycosis↗
PubMed1989

The association of posterior capsular lens opacities with bilateral acoustic neuromas in patients with neurofibromatosis type 2.

This study of 47 patients from 11 families with neurofibromatosis type 2 (NF 2) confirms our previously reported association between posterior capsular cataract and NF 2. A highly significant statistical association was found between the presence of posterior capsular lens opacities and the presence of NF 2 as determined by magnetic resonance imaging or pathologic diagnosis. This association was not present for other types of lens opacities that could be the result of age-related or nonspecific changes. When considering the diagnosis of NF 2, this finding now makes it essential to use a careful dilated biomicroscopic examination of the lens to evaluate known, suspected, or at-risk individuals for this potentially early associated manifestation.

Cataract↗
PubMed1986

Main excretion metabolites of 7-methoxy-2-nitronaphtho[2,1-b]furan (R 7000) in rats.

Major metabolites, isolated from rat bile and urine after administration of a single dose of 7-methoxy-2-nitronaphtho[2,1-b]furan (R 7000; MNNF) labelled with 14C on the furan ring and on the methoxy group, were identified by comparison of their chromatographic behaviour and mass spectra with synthetic authentic reference compounds. Analysis of metabolites indicated three metabolic pathways for this compound in vivo, namely, demethylation of the methoxy group, hydroxylation of the aromatic ring and cleavage of the furan ring, followed by the reduction of the nitro group to amine.

Administration, Oral↗
PubMed1985

New cysteamine (2-chloroethyl)nitrosoureas. Synthesis and preliminary antitumor results.

Three chemical pathways were used for the synthesis of four new N'-(2-chloroethyl)-N-[2-(methylsulfinyl)ethyl]- and N'-(2-chloroethyl)-N-[2-(methylsulfonyl)ethyl]-N- or N'-nitrosoureas. These compounds are plasma metabolites of CNCC, a promising antineoplastic (2-chloroethyl)nitrosourea. Preliminary antitumor evaluation was performed against L1210 leukemia implanted intraperitoneally in mice. Among these compounds, two of them exhibited a greater antitumor activity compared to that of the parent mixture.

Animals↗
PubMed1985

Identification of oenanthotoxin and related compounds in hemlock water dropwort poisoning.

The case histories are presented of three separate incidents of poisoning by ingestion of Hemlock Water Dropwort tubers (Oenanthe crocata). Two of these cases involved a fatality. An analytical profile is provided for oenanthotoxin, the major toxic principal of the tubers. Chromatographic, spectroscopic and mass spectral data for related compounds are also given.

Adult↗
PubMed1985

Disposition in rats and mice of 7-methoxy-2-nitronaphtho[2,1-b]furan.

The disposition of 7-methoxy-2-nitronaphtho[2,1-b]furan (MNNF), labelled with 14C in the furan ring (label 1) and in the methoxy group (label 2) has been studied in rats and mice. After i.p. administration to rat (5 mg/kg), both labelled species were absorbed by the lymphatics; and after oral administration, through the intestinal lumen. Excretion of the furan ring (label 1) is mainly urinary (44% dose in 24 h); label 2 was mostly expired as 14CO2 (48% dose in 24 h), indicating considerable demethylation. No target organ was found for MNNF, except liver and kidney. For both labelled species given orally, radioactivity was bound to the intestinal wall. Preliminary metabolic studies, using t.l.c. and h.p.l.c., have shown the presence of an urinary metabolite, namely, the glucuronide of 7-hydroxy-2-nitronaphtho[2,1-b]furan (15-20% of the urinary radioactivity). The remaining radioactivity comprises basic compounds, that bind to a cationic resin, which might be formed by enzymic reduction of the nitro group.

Administration, Oral↗
PubMed1984

Nucleic acid metabolism in the nucleus and cytoplasm of angiosperm meiocytes.

Over the course of flowering plant evolution many important stages in the life cycle have become compressed into the period between the premeiotic mitosis and gamete maturation. For this reason the changes in structure or chemistry that take place at this time are not easily ascribed to particular 'developmental stages'. During the meiotic process itself striking changes occur in levels of cytoplasmic and nuclear RNA, while DNA is synthesized in both the chromosomes and organelles. Evidence is presented indicating that a large proportion of the m- and rRNA is purged from the meiocyte cytoplasm by a combination of normal degradation and the activity of specific hydrolases. DNA synthesis in both the plastids and mitochondria precedes the re-differentiation of these organelles, while that in the chromosomes occurs in two major peaks, as has previously been reported (Hotta & Stern, 1971). High-resolution autoradiography did not indicate either peak of DNA synthesis to be localized within the synaptonemal complex, although final confirmation of this conclusion must await further investigation. Examination of these events in organisms where meiosis is removed from other stages of the life cycle suggests that the degradation of RNA and the chromosomal DNA synthesis are features which regularly accompany the meiotic process. The significance of these findings is discussed in terms of the hypothesis that there is at least one stage in the life cycle of all plants at which a purge of information-carrying molecules takes place.

Cell Differentiation↗
PubMed1983

Changes in poly(a)+ RNA during male meiosis in Lilium.

Levels of poly(A)+ RNA have been investigated at each stage of male meiosis in Lilium (var. Firecracker). Two methods were employed in this work: in one extracts from labelled meiocytes were passed through oligo(dT) columns, while in the other the specific probe [3H]poly(U) was hybridized in situ with resin-embedded sections of pollen mother cells. The label contained in the eluate from the oligo(dT) columns was measured by liquid scintillation, and the quantity of [3H]-poly(U) hybridized was determined by statistical analysis of light microscopic autoradiographs. Both techniques revealed a dramatic decline in detectable poly(A)+ RNA during prophase. Lowest levels are reached in the pachytene stage, following which a gradual restoration of this species of RNA takes place in both nucleus and cytoplasm. The data presented here provide no clear indication as to whether this fall in RNA levels is caused by the action of novel enzymes specific to the meiotic prophase, by a cessation of synthesis and the activity of normal turnover processes, or by a combination of the two. Although there is some evidence from the [3H]poly(U) hybridization study that a small peak of poly(A)+ RNA synthesis may take place in leptotene, both methods indicate that there is a very low of poly(A)+ RNA synthesis throughout prophase. The presence of poly(A)+ RNA was not detected in either the accessory nucleoli or the cytoplasmic nucleoloids that characterize the nucleus and cytoplasm of these cells. These events are considered in terms of the juncture at which they occur in the plant life-cycle.

Meiosis↗
PubMed1982

The fetal soul.

Explore the source record for details and available documents.

Catholicism↗
PubMed1982

Ultrastructural and enzymatic development of fetal guinea pig heart.

The activities of some enzymes of glycolysis, the citric acid cycle, and amino acid metabolism have been measured in the fetal guinea pig heart over the last third of gestation and correlated with heart ultrastructural development. There is little change in glycolytic enzyme activity except for a two- to threefold increase in phosphofructokinase activity. Mitochondrial content and enzyme activities are low in the early fetal heart, and, although content is similar in the late fetus and adult, enzyme activities increase twofold postnatally, indicating fetal heart mitochondria are incompletely developed. The activities of aspartate and particularly alanine aminotransferase are low in the fetal heart. Over the last third of gestation the myofibrillar content of the fetal myocyte increases twofold to the adult value by term. Associated with this is a fourfold rise in myofibrillar and sarcoplasmic reticulum Ca2+-ATPase activity. Na+-K+-ATPase activity is similar in the late fetal and adult heart but one-third lower in the early fetal heart.

Adenosine Triphosphatases↗
PubMed1982

Distribution of 125I-labelled follicle-stimulating hormone and human chorionic gonadotrophin in the gonads of hypogonadal (hpg) mice.

Hypogonadal mice are deficient in LH releasing hormone (LH-RH), the releasing factor for LH and FSH, with a consequent failure of postnatal ovarian and testicular development. After intravenous injection of hypogonadal females with 125I-labelled human chorionic gonadotrophin (hCG), followed by autoradiography of semi-thin (1 micrometer) slices of the ovary, labelled hCG was found to be associated with interstitial cells and thecal cells with little or no labelling of granulosa cells. Labelled human FSH was associated solely with granulosa cells. Hypogonadal females, implanted for 5 days with a silicone elastomer capsule of oestrogen, showed a similar response to that of normal females with hCG labelling of the granulosa cells of the larger follicles as well as of the thecal cell layer. Furthermore, subcutaneous injection of hypogonadal females with LH-RH (50 ng), 12 times daily for 5 days, increased uterine weight and stimulated ovarian development with some large follicles binding hCG to both thecal and granulosa cells. Therefore stimulation of follicular development may possibly be associated with increased oestradiol concentrations. In the male, after injection of 125-I-labelled hCG, silver grains were associated with the interstitial cells alone in both hypogonadal and normal mice. Labelled human FSH was undetectable in semi-thin testicular sections, but the mode of injection (intravenous) not have allowed enough labelled hormone to reach the testis in order to resolve the question as to whether the hypogonadal or normal testis can bind FSH.

Animals↗
PubMed1976

Cholecystostomy.

The role of cholecystostomy in the sugical treatment of gallstones has been considered. In a consecutive series of 558 patients who underwent surgery for gallstones, 30 (5-4 per cent) had cholecystostomy alone and a further 17 (3-1 per cent) cholecystostomy combined with exploration of the bile ducts. Cholecystostomy was done because cholecystectomy was technically very hazardous in 15 patients. In the remaining patients cholecystostomy was preferred to cholecystectomy because o f the poor general condition of the patient or the presence of pancreatitis. Of the 47 patients submitted to cholecystostomy, 2(4-2 per cent) died postoeratively and 4(8-4 percent) subsequently underwent cholecystectomy. Of 24 patients who were available for long term follow-up, only 1 patient had pain which was definitely considered to be due to gallstones, although 3 other patients also had abdominal pain, while 7 patients showed radiological evidience of gallstones. It is contended that cholecystostomy has a small but definite part to play in the immediate surgical treatment of gallstones and that the long term results of the operation are sufficiently good to justify its use in selected patients.

Adult↗