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Biomedical subjects

J Yates

Publications and source records attributed to J Yates.

At least 109 records · Page 6Linked to original sources

Role of hypertension and coagulation in the progressive glomerulopathy of rats with subtotal renal ablation.

Administration of heparin to rats with 1 3/4 nephrectomy prevents the development of glomerulosclerosis, hypertension and retards the decrease in renal function seen in these rats. To further define the role of hypertension and/or coagulation in the pathogenesis of the glomerulopathy seen in this model we studied several groups of rats with 1 3/4 nephrectomy: (1) a control group; (2) a group receiving a 'high dose' of acetylsalicylic acid (50 mg/kg) plus dipyridamole (10 mg/kg); (3) a group receiving a 'low' dose (5 mg/kg body weight) of acetylsalicylic acid alone; (4) a group receiving OKY 1581, an inhibitor of thromboxane synthesis; (5) a group treated with antihypertensive medications; (6) a group receiving heparin subcutaneously twice daily, and (7) a group given oral Coumadin. Drugs in all groups were administered daily for 4 weeks. All treated groups had a decrease in blood pressure (BP), in the ratio of heart weight to body weight, in BUN levels and had fewer abnormal glomeruli. The effects of acetylsalicylic acid alone, of acetylsalicylic acid plus dipyridamole, and OKY 1581 may be due to inhibition of platelet aggregation and intraglomerular thrombosis, with the fall in BP being the consequence of improved renal function. On the other hand, the decrease in BP may be related to a primary effect of these drugs. The lower BP in turn may play a role in slowing the progression of renal disease and improving the renal histology in the treated groups.

Animals↗

Thromboxane synthesis and blood pressure in spontaneously hypertensive rats.

The present study examines effects of administration of OKY 046, an inhibitor of thromboxane synthesis, for 100 days on systemic blood pressure and renal function in spontaneously hypertensive rats and in normotensive control rats. Untreated spontaneously hypertensive rats had higher values for thromboxane excretion in the urine and higher values for blood pressure than did normotensive control rats. Administration of OKY 046 decreased systolic and mean arterial blood pressure and urinary excretion of thromboxane and protein in spontaneously hypertensive rats. Administration of OKY 046 decreased thromboxane excretion in the urine of normotensive control rats but had no effect on blood pressure or protein excretion. Renal function, as assessed by the clearances of inulin and p-aminohippuric acid, was greater in spontaneously hypertensive rats treated with OKY 046 than in those receiving vehicle alone. In normotensive control rats, OKY 046 administration did not affect renal function. These results suggest that increased renal synthesis of thromboxane may play a role in the pathogenesis of the elevated blood pressure of spontaneously hypertensive rats.

Acrylates↗

In vivo evaluation of myocardial infarction by computed tomography: an experiment with electrocardiographic gating.

Retrospectively gated and ungated images of normal and 24 h post-infarction mini-pig hearts were obtained. The 11 imaged infarcts were transcatheter embolisation of the branches of the left anterior descending coronary artery. Using a contrast infusion technique and scanning during infusion, four infarcts were clearly detected as low-attenuation areas in the myocardium, one of these showing adjacent contrast enhancement. Two other infarcts showed as enhancing regions. Two small infarcts (0.8-1.0 cm3) were not detected and three others were in doubt. Streaking and other artefacts presented difficulties in image interpretation, which were sometimes resolved by gating. A comparison is made of these findings with those obtained from experiments with dogs, of comparable methodology. Differences are considered to result from anatomical differences between the two species, more particularly in the collateral blood supply to the myocardium.

Animals↗

Presenting conditions of 1539 population-based lung cancer patients by cell type and stage in New Hampshire and Vermont.

The authors identified all newly diagnosed lung cancer cases in New Hampshire and Vermont for the period 1973 through 1976 and abstracted clinical data on presenting symptoms and findings from their hospital records. Microscopy slides were also reviewed, when possible, to confirm cell type. The most frequent presenting symptoms were weight loss (46%) and cough (45%). Other common symptoms were dyspnea (37%), weakness (34%), chest pain (27%), and hemoptysis (27%). The presence of symptoms and findings was in general related to disease stage but bore little relationship to cell type. These results differ from those of previously reported case series that were based on surgical, radiation therapy, or Veterans Hospital groups, but the current data agree closely with those from another population-based series in Finland.

Adenocarcinoma↗

Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal renal ablation.

Ablation of greater than 70% of renal mass in the rat results in hypertension, proteinuria, and glomerular sclerosis of the remnant kidney. Rats with a remnant kidney have increased excretion of thromboxane in the urine when compared with normal rats. Chronic oral administration of OKY 1581, an inhibitor of thromboxane synthesis, in rats with a remnant kidney increases renal blood flow and glomerular filtration rate (GFR), decreases protein and thromboxane excretion in the urine, lowers blood pressure and cardiac index, and improves renal histology. The degree of hypertrophy of the remnant kidney was unaffected by administration of OKY 1581. Calculated values for single nephron plasma flow and GFR were significantly greater in rats with remnant kidneys given OKY 1581 than in rats given saline. Acute i.v. administration of OKY 1581 increased renal plasma flow and GFR in rats with a remnant kidney but not in normal rats or rats with a remnant kidney previously treated with acetylsalicyclic acid. OKY 1581 markedly inhibited platelet aggregation. We suggest that in this model of renal disease platelet aggregation and intraglomerular thrombosis play a key role in the development of glomerulosclerosis. Inhibition of platelet aggregation prevents development of glomerulosclerosis, hypertension, and cardiac hypertrophy. We suggest that hyperperfusion and hyperfiltration per se occurring in remnant glomeruli are not directly responsible for the development of glomerulosclerosis.

Acrylates↗

A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus.

Epstein-Barr virus (EBV) transforms human B-lymphocytes into proliferating blasts which are efficiently established into cell lines. The viral DNA in these cell lines is usually present as complete, unintegrated plasmid molecules. A cis-acting element of EBV, oriP, permits plasmid maintenance in adherent cells that carry EBV DNA. We constructed a vector, pHEBo, that carries oriP and showed that it is also efficiently maintained as a plasmid when introduced into EBV-transformed B-lymphoblasts. The pHEBo vector carries the coding sequences for the hph gene from Escherichia coli such that it can be expressed in mammalian cells and confers resistance to the antibiotic hygromycin B. Hygromycin B kills EBV-transformed lymphoblasts at concentrations of 50 to 300 micrograms/ml. The combination of oriP plus the expressed hph gene makes pHEBo useful for the stable introduction of genes on plasmids into EBV-transformed lymphoblasts. Because pHEBo is derived from the plasmid pBR322 it can be easily isolated from lymphoblasts by reintroduction into E. coli.

B-Lymphocytes↗

A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components.

A genetic element of Epstein-Barr virus, oriP, when present on recombinant plasmids allows those plasmids to replicate and to be maintained in cells that express the Epstein-Barr virus-encoded nuclear antigen EBNA-1. Here we define the DNA sequences required for oriP activity. Two noncontiguous regions of oriP are required in cis for activity. One consists of approximately 20 tandem, imperfect copies of a 30-base-pair (bp) sequence. The other required region, approximately 1,000 bp away, is at most 114 bp in length and contains a 65-bp region of dyad symmetry. When present together on a plasmid, these two components supported plasmid replication even when the distance between them was varied or their relative orientation was altered, or both. When present alone on a plasmid that expresses a selectable marker, the family of 30-bp repeats efficiently conferred a transient drug-resistant phenotype in human 143 cells that is dependent on the presence of EBNA-1. This result leads us to suggest that EBNA-1 interacts with the 30-bp repeated sequence to activate oriP. To test whether the 30-bp repeats might cause the increased transient expression of drug resistance by enhancing transcription, the family of 30-bp repeats was tested for the ability to activate the simian virus 40 early promoter present in plasmid pA10CAT2 (Laimins, et al., Proc. Natl. Acad. Sci. U.S.A. 79:6453-6457). In this assay, the 30-bp repeats could activate the simian virus 40 early promoter in Raji cells, an EBNA-positive Burkitt's lymphoma cell line, but not detectably an EBNA-positive 143 cells in which oriP also functions.

Acetyltransferases↗

Dietary protein intake conditions the degree of renal vasoconstriction in acute renal failure caused by ureteral obstruction.

Whole kidney inulin (CIn) and PAH (CPAH) clearances were measured after unilateral release of bilateral ureteral obstruction (BUO) of 24-h duration in rats fed for 4 wk isocaloric diets containing either 40% casein (high protein diet) or 6% casein (low protein diet). Values for CIn and CPAH were markedly depressed in both groups but to a greater extent in high protein-fed rats, averaging less than 60% of values measured in low protein-fed animals. Captopril, an inhibitor of the angiotensin I converting enzyme, increased CIn and CPAH markedly but comparably in high or low protein fed rats. Micropuncture studies performed after unilateral release of BUO in another group of rats fed a high or a low protein diet revealed lower levels of glomerular plasma flow rate (QA) and single nephron glomerular filtration rate (SNGFR) in rats fed a high protein diet. Values for renal arteriolar resistances were nearly twofold in high as compared with low protein-fed animals. Infusion of OKY-1581, an inhibitor of thromboxane A2 synthetase, increased both QA and SNGFR, decreased arteriolar resistances, and increased glomerular capillary ultrafiltration coefficient in high but not in low protein-fed rats. Urinary thromboxane B2 excretion per milliliter of GFR was greater in rats fed a high protein diet than in those fed a low protein diet after release of BUO but not in normal rats. In normal rats infusion of OKY-1581 did not increase CIn or CPAH.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells.

The Epstein-Barr viral (EBV) genome of approximately equal to 170 kilobase pairs (kbp) is maintained as a plasmid in human B lymphoblasts transformed by the virus. We have identified a cis-acting element within 1.8 kbp of the viral genome that allows recombinant plasmids carrying it to be selected at high frequency and maintained as plasmids in cells latently infected by EBV. This functional element(s) requires a segment of DNA at least 800 bp and at most 1800 bp long, which contains a family of 30-bp tandem repeats at one end. Since this region confers efficient stable replication only to plasmids transfected into cells containing EBV genomes, its function probably requires trans-acting products encoded elsewhere in the viral genome.

DNA Replication↗

Transforming functions associated with Epstein-Barr virus.

Epstein-Barr virus (EBV) transforms the human B-lymphocytes it infects into lymphoblasts that are competent to proliferate indefinitely in tissue culture [1]. The dividing transformed lymphoblasts carry multiple and complete copies of EBV DNA as plasmids [1]. No viral functions that are necessary for EBV-induced transformation have been identified and characterized to date. We have developed an assay that aids in the identification of viral functions needed to maintain the viral plasmid in transformed cells. The assay employs a plasmid vector that encodes resistance to ampicillin and can replicate in E. coli. It also encodes resistance to the neomycin derivative G418, so that its presence can be selected in mammalian cells [2]. Fragments of viral DNA that span the genome have been molecularly cloned into this vector. These recombinant molecules have been transfected into four cell types, and survivors to G418 have been scored. The DNA from one region of EBV gives a 10- to 100-fold higher rate of survival per microgram of added DNA than does the DNA from all other recombinants, as tested in cells that already contain EBV genomes. This recombinant fragment of EBV is maintained in an apparently unrearranged state as a plasmid and therefore carries at least those cis-acting viral elements necessary for plasmid replication.

B-Lymphocytes↗

Calcium hydroxide pulpotomy for primary teeth: a clinical study.

Calcium hydroxide pulpotomies were performed in 17 carious primary mandibular molars. Variables in the pulpotomy procedure were recognized and controlled in an attempt to obtain a more favorable result or end product. The effects of two methods of hemorrhage control were also evaluated. The duration of treatment for the study ranged from three to nine months. Treatment was clinically successful for all 17 teeth. The radiographic evaluations were more favorable for the experimental group than for the control group. Treatment was radiographically successful for 15 teeth, questionable for one tooth, and unsuccessful for one other tooth. The results of this study suggest that the aluminum chloride-calcium hydroxide pulpotomy may be a viable alternative to formocresol pulpotomies in the primary dentition. Although these findings encourage continued research, including a long-term follow-up, a histologic study is indicated.

Aluminum↗

Incidence of lung cancer by cell type: a population-based study in New Hampshire and Vermont.

Identified were 1,906 cases of confirmed lung cancer that occurred among all residents of New Hampshire and Vermont over a 4-year period. Medical records, pathologists' reports, and, when possible, pathology slides were obtained and reviewed to assign cases to a specific histologic diagnosis. The diagnosis made by the original pathologist was generally confirmed upon review, except for the large cell undifferentiated cell type which appeared to be an unreliable classification. Among men at all ages incidence rates for squamous cell cancer far exceeded those for adenocarcinoma and small cell undifferentiated carcinoma, and the three age-incidence curves showed a similar pattern, rising until the eighth decade of life and then declining. Among women these three major cell types occurred about equally often, but the age-incidence curves differed in shape with adenocarcinoma reaching a peak incidence at an earlier age.

Adenocarcinoma↗

Effects of prostacyclin on short-circuit current and water flow in the toad urinary bladder.

The effects of prostaglandins of the E series on sodium and water transport have been studied extensively. PGE2 has been shown to inhibit the increase in osmotic water flow produced by vasopressin and to stimulate short-circuit current (SCC) in the toad bladder. On the other hand, the effects of prostacyclin (PGI2), an arachidonic acid product, on sodium and water transport have not been extensively evaluated. The present studies describe the effects of PGI2 on basal and vasopressin-stimulated osmotic water flow and on SCC in the urinary bladder of the toad. Studies were performed in the absence or presence of indomethacin. PGI2 in the absence of indomethacin had no effect on basal or vasopressin-stimulated osmotic water flow. When indomethacin was present, thereby eliminating intrinsic prostaglandin biosynthesis, PGI2 inhibited basal but not vasopressin-stimulated osmotic water flow. PGI2 increased SCC in the presence or absence of indomethacin. 6-keto PGF1 alpha, the stable metabolite of PGI2, had no effect on SCC. PGI2 stimulated cAMP production in isolated toad bladder epithelial cells. 2',5'-Dideoxyadenosine, an inhibitor of cAMP production, blocked the increase in SCC produced by PGI2, suggesting that the effects of this compound on SCC are mediated via cAMP.

1-Methyl-3-isobutylxanthine↗

Effect of estradiol on human breast cancer cells in culture.

Conditions are described for growing and maintaining the estradiol sensitivity of the human breast cancer cell line ZR-75-1 both in monolayer and suspension cultures. Either newborn calf or fetal calf serum can be used in the culture medium, but an effect of estradiol on growth of the cells was only observed reproducibly if the serum was first treated with dextran-charcoal. Sulfatase treatment of the sera prior to dextran-charcoal treatment did not decrease cell growth in the absence of added estradiol, indicating that estrogen sulfates are unlikely to contribute to cell growth in dextran-charcoal-treated sera. In monolayer cultures, estradiol increased both the growth rate and final saturation density of the cells for each individual plating density tested in a dose-dependent manner with maximal stimulation occurring between 10(-10) and 10(-8) M estradiol. Estradiol also markedly increased the ability of the cells to grow both in suspension and semisolid Methocel cultures. In suspension, the cells grew as tight balls which clustered together to give small organoid-like structures reaching diameters of 4 mm and composed of an outer shell of living cells containing a central cavity of necrotic cells. In the absence of estradiol in both monolayer and suspension, the cells went through a limited and constant number of divisions and then stopped, such that the final cell number was determined by the initial plating density. In the presence of estradiol, this block was removed such that in monolayer cultures the final cell number was independent of plating density. A major loss of estradiol response was found if the cells were grown for 7 to 14 days in the absence of estradiol. This loss of response appeared to be due to a loss of ability to grow rather than to selective cell death within the population.

Breast Neoplasms↗