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C Wheeler

Publications and source records attributed to C Wheeler.

At least 91 records · Page 5Linked to original sources
PubMed1987

Hormonal regulation of rat uterine secretory protein synthesis.

Treatment of the rat uterus with estradiol results in many morphological and biochemical changes. In order to examine the biochemical mechanisms of these changes, we are interested in finding a protein which can be used as an end-point indicator or marker. Estradiol administration results in the increased synthesis and release of a 115,000 and 65,000 dalton protein into the incubation media. In this paper, we demonstrate that these proteins are actually subunits of a larger protein having a molecular weight of 180,000 daltons. This protein appears to be specific to the uterus and may be produced mainly or solely by the epithelial cells. In the normal estrous cycle, maximal production is seen at estrus with essentially no production at diestrus. In the immature rat, synthesis of the 180K dalton protein is blocked by the interaction of progesterone and estradiol. However, unlike some uterine responses, the 180K protein is increased by treatment with several antiestrogens. This protein is also present in sufficient quantities to allow for the production of monoclonal antibodies. Thus this protein has many attributes of an excellent "marker protein" and will be of value in future studies aimed at elucidating the molecular mechanism(s) of steroid hormone action in the uterus.

Animals↗
PubMed1987

Estrogen regulation of protein synthesis in the immature rat uterus: the effects of progesterone on proteins released into the medium during in vitro incubations.

We have previously identified two major medium proteins secreted from the rat uterus during in vitro incubations that appear to be estrogen regulated. In this study, immature rats were treated with estradiol (E2) progestins, and actinomycin D. Medium proteins were analyzed after incubation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. E2 (1 microgram) increased the synthesis of proteins with mol wt of 115,000 and 65,000. Progesterone inhibited this increase when given in doses of 500 and 250 micrograms and when given within 8 h of estradiol. Lower doses of progesterone were not completely inhibitory. When actinomycin D was given within 6 h of E2, it also inhibited the E2 stimulated increase. This system may provide a useful marker for monitoring hormonal action in the luminal epithelium and may help in understanding hormonal regulation of gene expression.

Animals↗
PubMed1987

Endometrial cytosolic and nuclear progesterone receptors in the luteal phase defect.

Basal body temperature profiles, serial serum progesterone levels, and serial endometrial biopsies were studied in 15 infertile women during 21 ovulatory cycles. Ten cycles (in 9 women) demonstrated luteal phase defects (LPD), diagnosed by a histological lag in endometrial maturation, normal luteal phase length, and normal luteal phase serum progesterone levels. Both normal and LPD cycles had a maximum amount of endometrial cytosolic progesterone receptor (PgR) on days 13-15, with a significant decline thereafter. LPD cycles had significantly lower endometrial nuclear PgR concentrations than did normal cycles during the proliferative phase, but luteal phase endometrial nuclear PgR levels were similar in both groups. In 2 LPD women treated with dydrogesterone, normal endometrial maturation and a decline in endometrial cytosolic PgR concentrations in the late luteal phase were found. Therefore, with the exception of endometrial nuclear PgR concentrations during the proliferative phase, we found no evidence for a major abnormality in endometrial PgR levels in LPD cycles with a lag in endometrial histology.

Adult↗
PubMed1987

Cervical mucus changes in relationship to urinary luteinizing hormone.

In order to evaluate the relationship between the urinary luteinizing hormone (LH) surge as detected by the OvuSTICK (Monoclonal Antibodies, Inc., Mountain View, CA) method and daily cervical mucus parameters, ten spontaneously ovulating women undergoing infertility evaluation were followed during their cycles with twice daily urinary LH testing as well as daily ultrasound, mucus evaluation, and hormonal assays of serum LH, progesterone (P), and estradiol (E2). Maximal cervical mucus scores, as determined using a modified Insler score, were noted to coincide consistently with the urinary LH surge as detected by twice daily testing and to precede ultrasound evidence of ovulation by 0 to 24 hours. Mucus scores rapidly declined in the 24-hour period following the urinary LH surge. Detection of the urinary LH surge may therefore help identify that period of time during which cervical mucus parameters are optimal and therefore facilitate the timing of artificial insemination, intercourse, or postcoital testing.

Cervix Mucus↗
PubMed1986

Prevention of anthracycline-induced cytotoxicity in hemopoietic cells by hemin.

Anthracyclines such as Adriamycin (ADR) and daunomycin markedly inhibit cell growth in vivo and in vitro. These studies demonstrate that 30 microM hemin, which induces hemoglobin synthesis in human and murine erythroleukemia cells in culture, markedly decreases the cytotoxicity of ADR in a variety of hemopoietic cell lines (K562, HEL-1, MEL-745, HL-60, and U937) and in erythroid burst-forming cells from normal human marrow. Hemin failed to protect four of the five nonhemopoietic cell lines tested, including MCF-, breast adenocarcinoma cells, C-205 colon carcinoma cells, mouse 3T3 fibroblasts, and mouse kidney VERO cells. Hemin did protect human neuroblastoma IMP-32 cells from ADR cytotoxicity; however, this nonhemopoietic cell line undergoes dendrite formation in response to hemin induction. Cytofluorographic analysis of cellular ADR content and labeling studies with [3H]daunomycin demonstrated that hemin decreases the intracellular accumulation of these anthracyclines by more than 50% in K562 erythroleukemia cells. These studies indicate that small doses of hemin prevent intracellular accumulation of anthracyclines and thereby markedly reduce anthracycline toxicity to cells. Since this protective effect is observed preferentially with hemopoietic cells, it is possible that this finding could be exploited to protect the bone marrow from the cytotoxic action of anthracyclines during therapy for nonhemopoietic tumors.

Animals↗
PubMed1985

BCG treatment of periocular sarcoid.

Twenty-six horses and five mules with periocular sarcoids were treated with intralesional injections of a purified bacillus of Calmette and Guerin (BCG) cell walls in oil suspension. All sarcoids were cured and the horses and mules remained free from recurrence of sarcoid during the two-year follow-up period.

Animals↗
PubMed1984

m-AMSA as a probe for transport phenomena associated with anthracycline resistance.

Kinetics of transport of the acridine derivative 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA) were examined in P388 murine leukemia cells and in P388/ADR, a subline selected for adriamycin resistance and cross-resistant to a variety of drugs including m-AMSA. Compared with the drug-responsive parent cell line, P388/ADR cells showed impaired accumulation of m-AMSA and an enhanced rate of drug exodus. Competition studies demonstrated structural specificity of the outward transport process. There was a low degree of intracellular m-AMSA binding, and steady-state drug levels were reached in less than 1 min. These results suggest that m-AMSA will be a useful probe for studying transport systems associated with anthracycline resistance.

Aminacrine↗
PubMed1984

Hepatitis A virus: growth characteristics of in vivo and in vitro propagated wild and attenuated virus strains.

Serial passage of the MS-1 strain hepatitis A virus (HAV) in marmosets was shown to increase the yield of virus and to shorten the incubation period from approximately 55 days in the first passage to 3-7 days in the ninth and higher passages. Intravenous inoculation of susceptible chimpanzees with MS-1 HAV was found to result in a typical course of disease in two animals who had received eighth marmoset-passage virus, including the occurrence of elevated ALT activity, presence of HAV antigen in liver and stool, and seroconversion to anti-HAV. Two chimpanzees inoculated with 20th passage MS-1 HAV (M001 liver homogenate) exhibited normal or nearly normal ALT activity and had no demonstrable or significant HAV in weekly liver biopsy specimens or in serial stool suspensions obtained during 64 days of observation. However, both animals seroconverted to anti-HAV within 2 weeks after inoculation, as did the animals who had received eighth passage MS-1 HAV. These findings suggest that subpassage of the MS-1 strain of HAV in marmosets resulted in the generation of an attenuated virus strain that was still capable of inducing a vigorous antibody response in intravenously infected chimpanzees. Serial propagation of wild and attenuated strains of HAV (HAS-15 and MS-1/M001, respectively) in FRhK-4 cells was associated with a significant decrease in the growth period for both viruses. Our studies have also shown that HAS-15 HAV can be recovered in maximum yield in later passages as early as 2 to 3 days after inoculation.

Animals↗
PubMed1984

The effect of zinc deficiency on prostaglandin synthesis in rat testes.

The effect of zinc deficiency on prostaglandin synthesis in rat testes was determined by feeding three groups of rats egg white-based semipurified diets. One group (ZD) was fed a zinc-deficient diet and two control groups were pair-fed (PF) or fed ad libitum (AL) a zinc-sufficient diet. The concentration (nanograms/gram) of the prostacyclin metabolite, 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha), in the tunica homogenate was significantly lower in ZD than in PF and AL groups. However, there was no difference when 6-keto-PGF1 alpha concentration was expressed as nanograms/milligrams of tunica protein. Tunica PGE2 concentrations (nanograms/gram) were not significantly altered by zinc deficiency. Concentrations of prostaglandins (PGs) in testis parenchyma were slightly higher in ZD probably as a result of increased levels of the precursor, arachidonic acid (AA). There was a highly significant correlation between PGE2 and AA in parenchyma phospholipids. PG synthesis was much greater in the tunica than in the parenchyma and prostacyclin appeared to be the major PG synthesized in both the tunica and parenchyma. It was concluded that PG synthesis is altered in the testes of zinc-deficient rats probably due to changes in concentrations of protein in the tunica and AA levels in parenchyma lipids.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Fatty acid composition of the testes of zinc-deficient rats: the effect of docosapentaenoic acid supplementation.

To determine if low levels of docosapentaenoic acid (22:5 omega 6), observed in the testis lipids of zinc-deficient rats, are related to some of the symptoms of zinc deficiency in rat testes, four groups of rats were fed egg white- and corn oil (CO)-based semipurified diets. One group was fed a zinc-deficient diet (ZDCO) and a control group was pair-fed a zinc-supplemented diet (PFCO). Two additional groups were treated in an identical fashion, but their diets were supplemented with 1% testis lipid (TL) containing 10-12% 22:5 omega 6 (ZDTL and PFTL). Testes weights and sperm counts were slightly higher in ZDTL compared to ZDCO, but these trends were not statistically significant. Testis zinc concentrations were significantly higher in both TL groups compared to the corresponding CO group. Dietary 22:5 omega 6 appeared to be accumulated in liver lipids; however, there was no difference between TL and CO groups in 22:5 omega 6 level in testes phospholipids or testes total lipids. These results indicate that 22:5 omega 6 concentration and spermatogenesis in the testes of zinc-deficient rats do not appear to be affected by the dietary supplementation of 22:5 omega 6 at the level used in this study.

Animals↗
PubMed1984

Zinc deficiency affects neither platelet arachidonic acid metabolism nor platelet aggregation in rats.

The effects of zinc deficiency on arachidonic acid (AA) metabolism and platelet aggregation were studied in rats. Concentrations of AA metabolites synthesized by collagen-stimulated platelets were greater in rats fed a zinc-deficient diet (ZD group) than pair-fed control rats (PF group). This difference appeared to be due to increased platelet number in the ZD group. Preincubation of platelet-rich plasma of ZD group with various concentrations of zinc sulfate, prior to the aggregation induced by collagen suspension, Affected neither concentrations of AA metabolites nor the degree of platelet aggregation. Contrary to a report by other investigators, ADP-induced platelet aggregation was not impaired in rats fed the zinc-deficient diet for 1 week or 5 days as compared to the pair-fed controls. Secondary phase aggregation was not observed during ADP-induced platelet aggregation regardless of concentrations of ADP, types and concentrations of anticoagulants used, routes of blood collection or types of dietary protein in this study. These results indicated that zinc deficiency does not seem to affect arachidonic acid metabolism or platelet aggregation in rats in relatively short-term studies.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1984

Genome size and complexity in Azotobacter chroococcum.

All of eight strains of Azotobacter chroococcum examined contained between two and six plasmids ranging from 7 to more than 200 MDal in size. Strain MCC-1, a derivative of NCIMB 8003, was cured of various of the four largest of its five plasmids and the phenotypes of the strains compared. all fixed nitrogen and exhibited uptake hydrogenase activity. No differences were observed in carbon source utilization or antibiotic, heavy metal or UV resistance. The genome sizes of two strains of A. chroococcum were determined by two-dimensional electrophoresis. Strain CW8, an isolate from local soil containing two small plasmids of 6 and 6.5 MDAl contained unique DNA sequences equivalent to 1.78 x 10(6) (+/- 20%) bp (1.2 x 10(9) Dal). In strain MDC-1, a derivative of MCC-1, containing a 190 MDal and 7 MDal plasmid, the genome size was 1.94 x 10(6) (+/- 20%) bp. In exponential batch cultures, both contained 20 to 25 genome equivalents per cell. MCD-1 exhibited complex UV kill kinetics with a marked plateau of resistance; CW8 showed a simple response inconsistent with the possibility of organization of its DNA into identical chromosome copies capable of independent segregation.

Azotobacter↗
PubMed1983

The cytochrome P-450 active site. Regiospecificity of prosthetic heme alkylation by olefins and acetylenes.

Hepatic microsomal cytochrome P-450 from phenobarbital-pretreated rats is inactivated during the metabolism of linear olefins (ethylene, propene, and octene) and acetylenes (acetylene, propyne, and octyne). As expected from previous work, the inactivation is due to N-alkylation of the prosthetic heme group by the substrate. The N-alkyl group in each adduct is formally obtained by addition of a porphyrin nitrogen to the terminal carbon and of an oxygen atom (as a hydroxyl function) to the internal carbon of the pi-bond. The oxygen is shown here by 18O studies to be catalytically introduced by the enzyme. The olefins exclusively alkylate the nitrogen of pyrrole ring D, but the acetylenes alkylate that of pyrrole ring A. Acetylene is an exception in that it reacts with more than one nitrogen. Circular dichroism studies of the ethylene adduct and of the ring D regioisomer of N-ethylprotoporphyrin IX obtained by alkylation of the prosthetic heme of hemoglobin have been used to determine which face of cytochrome P-450 heme is alkylated by the unsaturated substrates. These results implicate an active site that is sterically encumbered in the region over pyrrole ring B and has a lipophilic binding site that accommodates chains of at least six carbon atoms over pyrrole ring C.

Acetylene↗
PubMed1983

Stereochemistry of cytochrome P-450-catalyzed epoxidation and prosthetic heme alkylation.

Oxidation of 1-octene by cytochrome P-450 results concurrently in formation of 1,2-oxidooctane and in N-alkylation by the catalytically activated olefin of the prosthetic heme group. The stereochemistry of trans-1-[1-2H]octene is retained during both transformations. This alkylation stereochemistry requires addition of the pyrrole nitrogen and the activated oxygen to the same side of the double bond, a reaction geometry opposite to that expected if the heme were alkylated by the epoxide metabolite. Stereochemical analysis shows that the S enantiomer of the epoxide is formed in slight excess over the R enantiomer by oxidation of the re and si faces, respectively, of the olefin, but that heme alkylation only occurs during oxidation of the re face. The stereochemical specificity of epoxidation and heme alkylation requires that (a) the two processes proceed by independent (probably concerted) mechanisms, or (b) the two processes diverge from a common acyclic intermediate.

Alkenes↗