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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 487 records · Page 27Linked to original sources
PubMed1994

Mouse ferritin H subunit gene. Functional analysis of the promoter and identification of an upstream regulatory element active in erythroid cells.

Ferritin synthesis is regulated at the translational level by iron, but it is likely that transcriptional regulation of H and L genes is responsible for tissue-specific distribution of H and L mRNAs. In order to define the regions important for transcriptional regulation of the mouse ferritin H gene, we have linked the promoter, including the transcription start site, and 5 kilobases of upstream sequence to a reporter gene (human growth hormone). This construct and a series of 5' deletion mutants have been used to transfect erythroid (K562, mouse erythroleukemia (MEL)) and hepatoma (HepG2) cell lines. Measurement of growth hormone in the culture medium and analysis of ferritin-growth hormone transcripts by a ribonuclease protection assay revealed that a 140-base pair minimal promoter is sufficient to confer a high level of expression to the reporter gene in both cell types. In addition, a 180-base pair fragment, lying 4.5 kilobases upstream of the ferritin transcription start site, functions like an inducible enhancer during N,N'-hexamethylene-bis-acetamide-induced differentiation of MEL cells. A perfect match to a consensus binding motif to the erythroid transcription factor NF-E2 is present in this regulatory element, but the mutant NF-E2 enhancer retains the inducible activity in stably transfected MEL cells, and the results from gel retardation assays suggest that protein-DNA complexes that form in vitro between the ferritin enhancer and MEL nuclear extracts do not contain NF-E2. Thus, nuclear factors that mediate inducibility of the ferritin enhancer remain to be identified.

Animals↗
PubMed1994

Sequence and expression of a monkey testicular transcript encoding tMDC I, a novel member of the metalloproteinase-like, disintegrin-like, cysteine-rich (MDC) protein family.

Full-length clones encoding a novel member of the metalloproteinase-like, disintegrin-like, cysteine-rich (MDC) family of proteins have been isolated from a monkey (Macaca fascicularis) testicular cDNA library. The encoded putative 82 kDa transmembrane protein (tMDC I) shows striking sequence similarity to other members of the MDC family including rat and monkey EAP I, guinea-pig PH-30 and human MDC protein, as well as a number of snake venom components.

Amino Acid Sequence↗
PubMed1994

Genetic evidence for an additional member of the metalloproteinase-like, disintegrin-like, cysteine-rich (MDC) family of mammalian proteins and its abundant expression in the testis.

Full-length clones have been isolated from a Macaca fascicularis cDNA library corresponding to a 2.65 kb mRNA present at high steady state levels in the testis. Sequence analysis suggests that the predicted translation product, tMDC II protein, represents a novel member of the metalloproteinase-like, disintegrin-like, cysteine-rich (MDC) family of mammalian proteins.

ADAM Proteins↗
PubMed1994

Sequence analysis of a mammalian phospholipid-binding protein from testis and epididymis and its distribution between spermatozoa and extracellular secretions.

The cellular origin of a soluble phospholipid-binding protein (PBP) in rat testicular and epididymal secretions has been investigated genetically and immunologically. PBP is ubiquitous in tissue cytosols but is not present in blood serum, lymph or milk. The relatively large amounts present in cauda epididymal plasma (CEP) and rete testis fluid suggested therefore that it may be secreted specifically by these tissues. However, when PBP cDNAs from testis and epididymis were cloned and sequenced, they did not contain a signal peptide and only one size of transcript was obtained on Northern blots of RNAs from liver, brain, placenta, testis and epididymis. Moreover, PBP could not be detected in sperm-free CEP from castrated, androgen-stimulated animals or in medium from Sertoli cell cultures. Spermatozoa, on the other hand, contained significant amounts of PBP that could be solubilized by washing cells in dissociating reagents or high-salt solutions. These results indicate that, contrary to previous interpretations, PBP is not secreted by classical pathways in either the testis or epididymis but that its presence in CEP and rete testis fluid is attributable largely to release from spermatozoa. Thus, spermatozoa have a significant influence on the composition of CEP as well as on the secretory and absorptive activity of the epididymal epithelium. A possible role for PBP in membrane biogenesis and maintenance of antigen segregation in spermatozoa is discussed.

Amino Acid Sequence↗
PubMed1994

Comprehensive discharge planning for the hospitalized elderly. A randomized clinical trial.

OBJECTIVE: To study the effects of a comprehensive discharge planning protocol, designed specifically for the elderly and implemented by nurse specialists, on patient and caregiver outcomes and cost of care. DESIGN: Randomized clinical trial. SETTING: Hospital of the University of Pennsylvania. PATIENTS: 276 patients and 125 caregivers. Patients were 70 years and older and were placed in selected medical and surgical cardiac diagnostic-related groups. MEASUREMENTS: Group differences in patient outcomes (length of initial hospital stay, length of time between initial hospital discharge and readmission, and rehospitalization rates) and charges for care (charges for initial hospitalization, rehospitalizations, health services after discharge, and nurse specialist services) were measured 2, 6, and 12 weeks after discharge. RESULTS: From the initial hospital discharge to 6 weeks after discharge, patients in the medical intervention group had fewer readmissions, fewer total days rehospitalized, lower readmission charges, and lower charges for health care services after discharge. No differences in these outcomes were found between the surgical intervention and control groups during this period. CONCLUSIONS: Study findings support the need for comprehensive discharge planning designed for the elderly and implemented by nurse specialists to improve their outcomes after hospital discharge and to achieve cost savings. The findings also suggest that this intervention had its greatest effect in delaying or preventing rehospitalization of patients in the medical intervention group during the first 6 weeks after discharge.

Aged↗
PubMed1994

Implementing findings of research.

There are unacceptable delays in the implementation of many findings of research. This results in suboptimal care for patients. A number of approaches may be effective in speeding up implementation, including evidence based guidelines, the influence of opinion leaders, and computer based decision support systems. An integrated approach to speeding up this process by means of a number of mechanisms is likely to be most effective. The results of systematic reviews of the research literature should be incorporated into programmes of continuing medical education and clinical audit. Professional associations have an important role to play in ensuring that research based information is included in educational activities and clinical guidelines. Purchasers of health care could promote the uptake of research findings during contract negotiations. Improved methods of informing health care users and the public about evidence of effectiveness could also have an impact. Policy makers should take more account of the results of research when formulating recommendations. Methods of improving the implementation of research findings require further investigation and greater resources devoted to them.

Diffusion of Innovation↗
PubMed1994

Rapid inhibition of the sperm protease acrosin by protein C inhibitor.

Heparin was found to be an allosteric modulator of the amidolytic activity of the protease acrosin. In the presence of saturating concentrations of heparin, there was a 4.9-fold decrease in the value of the Michaelis constant for the substrate D-Ile-Pro-Arg-p-nitroanilide and the value of kcat was 2.5-fold lower. Analysis of the data yielded a dissociation constant of 0.22 +/- 0.04 microM for the heparin-acrosin complex. The presence of relatively high concentrations of protein C inhibitor in seminal plasma [Laurell, M., Christensson, A., Abrahamson, P., Stenflo, J., & Lilja, H. (1992) J. Clin. Invest. 89, 1094-1101] suggests that this serpin may be involved in the control of the activity of acrosin. Acrosin was found to be rapidly inhibited by protein C inhibitor with the association rate constant (kass) for the formation of the complex being (2.41 +/- 0.03) x 10(5) M-1 s-1. The value of kass showed a bell-shaped dependence on the concentration of heparin; it was maximal at concentrations of heparin between 0.08 and 3 microM and decreased at lower and higher concentrations. At the optimal heparin concentration, the value of kass for the acrosin-protein C inhibitor reaction was 230-fold higher ((5.6 +/- 0.1) x 10(7) M-1 s-1) than in the absence of heparin. The results suggest that protein C inhibitor may be important in the physiological control of acrosin activity, particularly where the presence of heparin-like glycosaminoglycans would stimulate the acrosin-protein C inhibitor reaction.

Acrosin↗
PubMed1994

The pharmacokinetics of p-Boronophenylalanine.fructose in human patients with glioma and metastatic melanoma.

PURPOSE: To study the biodistribution of p-Boronophenylalanine in patients undergoing surgery for intracranial tumors or metastatic melanoma. METHODS AND MATERIALS: D,L-p-Boronophenylalanine was administered as boronophenylalanine.fructose in an intravenous bolus 1-4 h before the operation. Blood samples were collected for 24 h from the time of administration of the compound, and the blood boron elimination parameters were determined. For the glioma patients tumor samples were obtained and skin, dura, periosteum, and surrounding brain samples were collected whenever possible. For the metastatic melanoma patients tumor, fat, skin, and muscle were collected. Determination of the boron content was performed using inductively coupled plasma-atomic emission spectrometry. Twelve melanoma patients and six glioma patients participated in the study. The melanoma patients included four cases of cutaneous metastatic melanoma, six cases of metastatic melanoma to the lymph nodes and two cases of cerebral metastasis. RESULTS: The results for the metastatic melanoma patients are encouraging with an average tumor:blood boron concentration ratio and standard deviation of about 4.4 +/- 3.2 and a maximum value of 10 for the cerebral metastasis. The glioma patients involved high grade glioma for which the tumor:blood ratio was 2.2 +/- 1.2. CONCLUSION: The tumor:blood ratios for melanoma fulfil requirements for epithermal boron neutron capture therapy for cerebral melanoma metastases, whereas those for high grade glioma do not.

Boron↗
PubMed1994

Crystal structure of a mispaired dodecamer, d(CGAGAATTC(O6Me)GCG)2, containing a carcinogenic O6-methylguanine.

The crystal structure of the synthetic deoxydodecamer d(CGAGAATTC(O6Me)GCG)2 has been determined and refined to an R-factor of 16.9% with data up to 2.9-A resolution. This sequence contains two mismatched base pairs between O6-methylguanine and adenine with the arrangement A(syn).(O6-Me)G(anti) which differs from the geometry observed in solution by NMR. The intermolecular arrangement is equivalent to the other isomorphous deoxydodecamers. However, the weakening of some significant crystal packing contacts was observed and related to the effect of stacking between the mispaired adenine and the adjacent guanine in the sequence. The structure is highly hydrated, with a total of 49 solvent molecules located. The methyl group and the mismatched base-pair geometry locally disrupt the B-DNA-type solvent network with two solvent molecules found close to the N1 and N6 of the mispaired adenine.

Adenine↗
PubMed1994

Fate of sperm organelles during early embryogenesis in the rat.

This report is part of a continuing study in which we employ monoclonal antibodies to membrane domains and internal organelles of rat spermatozoa in order to trace events during maturation, capacitation, fertilization, and early development. In the present study, we have used immunocytochemistry at the light and EM levels to localize one antibody, 5A5, to the fibrous sheath and a second, 3D5, to the outer mitochondrial membrane. Antibody 5A5 does not stain the fibrous sheath of spermatozoa of rodents other than the rat, while 3D5 can be localized to the outer mitochondrial membrane of rat, hamster, and mouse spermatozoa. In order to follow these antibodies during fertilization and early embryogenesis, we developed a method to stain internal components of zygotes and early embryos. Our findings suggests that the fibrous sheath disappears prior to the first cleavage and that mitochondria can be detected up to the 2-cell stage in mouse and the 4-cell stage in rat.

Animals↗