Search PubMed⌕ Search

Biomedical subjects

J D Kelly

Publications and source records attributed to J D Kelly.

At least 73 records · Page 4Linked to original sources

Relative platelet-derived growth factor receptor subunit expression determines cell migration to different dimeric forms of PDGF.

Platelet-derived growth factor (PDGF) receptor transfectants of a fibroblastoid cell line (BHK) have been used to investigate the ability of the three dimeric forms of PDGF to elicit a chemotactic response. Cells transfected with the beta receptor subunit were only responsive to PDGF-BB, whereas cells expressing the alpha-receptor subunit were equally responsive to all three dimeric forms, PDGF-AA, PDGF-AB, and PDGF-BB. A positive chemotactic response correlated with rearrangement of actin organization. In a study of human arterial smooth muscle cells that express both PDGF receptor subunits endogenously, we again found that recombinant PDGF-AA could elicit a chemotactic response. However, the two smooth muscle cell isolates we examined differed in their chemotactic response to PDGF-AA. This difference correlated closely with their ability to respond mitogenically to this PDGF dimeric form, and the magnitude of both chemotactic and mitogenic responses was related to the proportion of the two receptor subunit species at the cell surface.

Animals↗

Follicular control of oviposition in the hen.

Ligation of the largest preovulatory follicle (F1) or the second largest preovulatory follicle (F2) delayed terminal oviposition for at least 2 h. Ligation of the fourth or fifth largest preovulatory follicle had no effect on the time of terminal oviposition. The conclusion reached was that some factor produced by the most mature follicles in the ovarian hierarchy influenced the timing of oviposition. Since the terminal oviposition occurs independently of ovulation, the authors concluded that the influence of the F1 and F2 follicles was independent of any preovulatory endocrine changes.

Animals↗

Characterization and in vivo distribution of 99mTc- and 111In-labelled magnetite.

Magnetite (Fe3O4) particles 0.1-0.5 microns in diameter doped with either 99mTc or 111In have been prepared and characterized by electron microscopy and Mössbauer spectroscopy. The time courses of their distributions after injection into rats were determined, including studies by gamma-camera imaging; the main targets were the liver and lung. The radiolabelled magnetic agents may be of value in research studies combining radio- and magnetic resonance imaging procedures.

Animals↗

Two classes of PDGF receptor recognize different isoforms of PDGF.

Previous studies involving platelet-derived growth factor (PDGF) have been based on the premise that a single cell-surface receptor binds all three isoforms of PDGF (AA, BB, and AB). It is now shown that two populations of PDGF receptor exist and can be distinguished by their ligand binding specificity. The B receptor binds only the BB dimer, whereas the A/B receptor binds AA, BB, and AB dimers. Human dermal fibroblasts appear to express seven times as much B receptor as A/B receptor. The B receptor is responsible for most PDGF receptor phosphorylation.

Binding, Competitive↗

Inflammation: imaging with Tc-99m HMPAO-labeled leukocytes.

Leukocytes labeled with technetium-99m hexamethylpropyleneamine oxime (HMPAO) were used in 100 patients: 32 with suspected inflammatory bowel disease, 17 with fever of unknown origin, 21 with suspected abdominal sepsis, 20 with suspected bone sepsis, seven with bronchiectasis, and three with recent myocardial infarction. The distribution of activity in patients subsequently shown not to have inflammatory bowel disease was similar to that previously described for indium-111-labeled leukocytes. However, in this study, activity was also seen in the kidneys and bladder and occasionally the gallbladder on both early (1-3 hours) and late (24 hours) views, and in the colon in late views. Migration of Tc-99m-labeled granulocytes was seen in inflammatory disease as early as 30 minutes after injection, while normal bowel activity was not seen before 4 hours. The sensitivity of Tc99m-labeled leukocytes in the detection of inflammation was 100%, the specificity was 95%.

Colitis↗

Accumulation of ascorbate in rat cerebellum.

Ultrafiltration and gel chromatography on Sephadex G-75 have revealed no evidence of ascorbate-binding to protein components of the soluble fraction derived from a tissue homogenate of rat cerebellum. Furthermore, partition studies have failed to detect any binding of ascorbic acid to structural components of rat cerebellum, as the ascorbate content of cerebellar tissue exhibited linear dependence upon the concentration of free vitamin in the surrounding medium (0.1 M phosphate, pH 6.5). The accumulation of ascorbic acid in rat cerebellum is discussed, therefore, in terms of an elevated intracellular concentration maintained by active transport of the vitamin across cerebellar tissue membranes.

Animals↗

Clinical experience with 99mTc-hexamethylpropylene-amineoxime for labelling leucocytes and imaging inflammation.

Hexamethylpropylene-amineoxime (HMPAO) forms a lipid-soluble neutral complex with 99mTc which is rapidly incorporated into leucocytes in vitro. In six patients with suspected or known inflammatory disease, a "mixed" leucocyte suspension isolated from 85 ml blood anticoagulated with acid-citrate-dextrose was labelled by 99mTc-HMPAO with a mean efficiency of 47% (SE2%), of which 78% (3) was taken up by granulocytes. Activity eluted more rapidly from other cell types in vitro than from granulocytes, which remained firmly labelled. Mean initial biodistribution of the label and granulocyte recovery in blood of 32% (8) at 30-40 min showed that the granulocytes were not significantly activated during labelling. All six patients were positive for inflammatory disease, as early as 30 min in five patients and at 3 h in the sixth; they all remained positive at 20-24 h. Four patients also received 111In-labelled "pure" granulocytes. In terms of detail, the 99mTc images were comparable or superior to the 111In images.

Adult↗

Ascorbic acid synthesis by the mammalian fetus.

Fetal rat liver can synthesize ascorbic acid after 16 days of gestation. Fetal kidney was inactive and neither fetal guinea pig liver nor kidney possessed ascorbic acid synthetic ability.

Animals↗

The B chain of PDGF alone is sufficient for mitogenesis.

The platelet-derived growth factor (PDGF) is a mitogen derived from human platelets consisting of two related polypeptides termed A and B chains. The entire B chain of PDGF is highly (96%) homologous to a portion of p28sis, the transforming protein of simian sarcoma virus. It has been suggested that p28sis exerts its transforming potential by mimicking the growth promoting activity of PDGF and stimulating the cell in an autocrine manner. We have directly examined the mitogenic potential of p28sis and the B chain homologous region by expressing these heterologous sequences in the yeast Saccharomyces cerevisiae. In our constructions, these proteins are encoded by portions of the v-sis gene. Expression and secretion from the yeast cell is achieved by using a yeast promoter and the alpha-factor pheromone secretory leader. The sis proteins thus expressed and secreted are immunoreactive with anti-PDGF antisera and are mitogenic for cultured fibroblasts. Furthermore, they mediate this mitogenic activity by specific binding to the PDGF cell surface receptor. Gel electrophoresis and cell binding analysis indicates that the mitogenic species is primarily a disulphide-bonded dimer. We are able to conclude that p28sis is a mitogen and that a polypeptide corresponding to the B chain alone is sufficient to account for the mitogenic activity attributed to PDGF.

Animals↗

Clinical evaluation of a technetium-99m bone imaging agent based on the vicinal diphosphonate 1,2-diphosphonoethyleneglycol (DPEG).

From a series of technetium-99m labelled agents based on a vicinal diphosphonic acid structure, the ligand 1,2-diphosphonoethyleneglycol (DPEG) was selected for clinical study on the basis of a biodistribution in rats which compared well with that of methylene disphonphonate (MDP). The 99Tcm-DPEG agent was assessed in ten patients in whom bone metastases had been demonstrated by 99Tcm-MDP imaging two to seven days previously. Visual comparison of the skeletal images obtained with the two agents revealed the same number of bone metastases at the same locations. Statistical analysis of the data revealed no significant differences between the two radiopharmaceuticals on the basis of lesion to soft tissue ratio and lesion to normal bone ratio, although a slightly higher lesion to soft tissue ratio was found for MDP than for DPEG (p less than 0.03). At least for the formulation tested, it is concluded that this new radiopharmaceutical based on the P-C-C-P structure does not possess diagnostic advantages over 99Tcm-MDP for the detection of bone metastases.

Aged↗

Ascorbic acid in fetal rat brain.

Ascorbic acid in fetal rat brain increases from 374 mg/g on the 15th day of gestation to 710 mg/g by the 20th day and remains at that level until birth. There is an 18% drop from this plateau after birth.

Age Factors↗

Ascorbic acid changes in brain.

The level of ascorbic acid in the brain of growing rats was not influenced by efforts to accelerate neural activity. Treatments used to depress neural activity included thyroidectomy which produced a 13%-20% loss of ascorbic acid in cortical and cerebellar tissue and diazepam which produced a significant rise in the cerebellum. Ethanol and barbital were without effect.

Animals↗

The binding of ascorbate to bovine serum albumin.

Ultrafiltration has been used to investigate the interaction of ascorbate with bovine serum albumin in 0.1 M sodium phosphate buffer, pH 6.5. The results are interpreted in terms of the binding of ascorbate to four equivalent and independent protein sites, governed by an intrinsic association constant of 2 600 +/- 700 M-1 at 20 degrees C, thereby providing evidence for specificity of the interaction over a range of vitamin concentration (0.08-1.5 mM) pertinent to the physiological situation.

Animals↗

A Drosophila metabolic gene transcript is alternatively processed.

We have determined the organization and transcription of a Drosophila DNA segment coding for the purine pathway enzyme, GAR transformylase. Because the transcript encoding this enzyme is very rare, we used a novel method for exon mapping without isolating a cDNA. Our results suggest a long polypeptide having multiple domains, with GAR transformylase at the COOH terminus preceded by an extensive repeat. Part of the same DNA segment specifies a shorter transcript, which consists of the same 5' exons but lacks the last three 3' exons. A polyadenylation signal within an intron allows this single gene to encode two polypeptides. We hypothesize that alternative processing of a transcript is a basis for channeling metabolic intermediates into two different pathways.

Acyltransferases↗

Transcription terminates in yeast distal to a control sequence.

We have investigated transcription termination on a segment of Drosophila DNA that complements a yeast adenine-8 mutation. Poly(A)+ RNA transcribed from this segment in yeast terminates at multiple sites clustered just beyond an AAUAAA sequence implicated in polyadenylation of higher eucaryotic messages. Deletion analysis indicates that, in yeast, this sequence is not required for polyadenylation. Rather, transcription termination is signalled by a region that is upstream of the AAUAAA sequence. At least part of the control region appears to be an 8-base pair (bp) sequence also found in the termination control region of the yeast CYC1 gene. Termination sites for the various deletions show a clear sequence preference. These sites occur in clusters at least 50 bp downstream of the control region, suggesting similarities between termination in yeast and p-dependent termination in bacteria.

Animals↗

Changes in resistance in mixed infections of susceptible and benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis passaged in sheep.

Benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis were each diluted with equal numbers of their respective susceptible genotypes and passaged in separate worm-free sheep. The progeny of the mixed susceptible and resistant infections were diluted with equal numbers of susceptible genotypes before passaging on two further consecutive occasions in worm-free sheep. In H contortus the amount of thiabendazole required to prevent a 50 per cent egg hatching (LC50) was reduced at each generation, but the reduction was significant (P less than 0.05) only at the third passage. In T colubriformis the LC50 for thiabendazole was reduced only at the first passage and thereafter remained constant. The reduction was not significant. In another experiment, the dilution with susceptible genotypes was made only at the first passage. Thereafter for two further generations the progeny produced from the mixed infection were passaged in worm-free sheep. In H contortus a reduced amount of thiabendazole was required to prevent a 50 per cent egg hatching at each generation, but did not reach a level of significance. The result for T colubriformis was identical to the continuous dilution experiment.

Animals↗

Ascorbic acid in neural tissues.

Large amounts of ascorbic acid were readily removed from neural tissue by washing with warmed saline solutions. In areas where the original level was highest, such as cortex and cerebellum, a higher percentage was removed than from areas of lower concentration, such as pons-medulla. The residual level in both types of tissue was similar. During scurvy, the ascorbic acid retained in the guinea pig brain is more readily removed by washing than is that of the normal brain.

Animals↗