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Biomedical subjects

R E Jones

Publications and source records attributed to R E Jones.

At least 127 records · Page 7Linked to original sources
PubMed1989

The administration of pharmacological doses of testosterone or 19-nortestosterone to normal men is not associated with increased insulin secretion or impaired glucose tolerance.

Excess androgen secretion and exogenous androgen administration may decrease insulin sensitivity and impair glucose tolerance. We examined the responses to an oral glucose tolerance test in 30 normal men before and after 6 weekly injections of androgen administered in a double-blinded study design. The men were randomly assigned to 1 of 4 treatment groups: testosterone enanthate (TE), 100 or 300 mg/week, or 19-nortestosterone decanoate (ND), 100 or 300 mg/week. Serum testosterone levels, measured 2-3 days after the last dose, did not change in the men given 100 mg TE/week, increased 3-fold in those given 300 mg TE/week, and decreased in both ND groups. All four groups had comparable reductions in serum LH levels. Weight increased significantly in all except the 100 mg TE/week group, but there was no change in waist to hip ratio in any group. In spite of the demonstrated biological effects of the doses of steroid administered, androgen administration for 6 weeks did not increase fasting serum glucose or insulin concentrations. There was also no increase in peak serum insulin levels and areas under the insulin and glucose response curves after a 100-g oral glucose load. However, the mean serum insulin area under the curve decreased significantly in the men given 300 mg ND/week. In contrast to the results of studies of 17-alkylated androgens, our results demonstrate that pharmacological doses of testosterone and the administration of 19-nortestosterone for 6 weeks do not impair glucose tolerance or alter insulin secretion in normal men.

Administration, Oral↗
PubMed1989

Cloning and expression of human leukocyte 5-lipoxygenase.

In conclusion, we have cloned a full-length cDNA for human leukocyte 5-LO from differentiating HL-60 cells. The complete amino acid sequence of 5-LO has been determined from the nucleotide sequence of the cDNA. Some interesting features of the sequence include potential lipid and Ca2+ binding sites and sequence homologies with other lipoxygenases. Human osteosarcoma cells transfected with the 5-LO cDNA expressed 5-LO and LTA4 synthase activities that were indistinguishable from those of the human leukocyte enzyme confirming that the cloned cDNA was the correct gene.

Amino Acid Sequence↗
PubMed1988

[Immunohistochemical studies of the histogenesis of dermatofibrosarcoma protuberans].

Paraffin-embedded tissue sections taken from 16 patients with dermatofibrosarcoma protuberans were stained by means of the peroxidase-antiperoxidase technique using antibodies against S 100 protein, NSE, Leu 7, lysozyme, alpha-1 antitrypsin, alpha-1 antichymotrypsin, cytokeratin, desmin, vimentin, and factor VIII. Most of the tumor cells showed positive reactions to vimentin. Only 1-3% of the cells within the tumor area answered to the histiocytic markers lysozyme, alpha-1 antitrypsin, and alpha-1 antichymotrypsin. The remaining antibodies investigated did not react with the tumor cells. Our results support a fibroblastic, and contradict a neural or histiocytic, histogenesis of dermatofibrosarcoma protuberans.

Antibodies, Monoclonal↗
PubMed1988

Characterization of cloned human leukocyte 5-lipoxygenase expressed in mammalian cells.

5-Lipoxygenase has been expressed in a mammalian osteosarcoma cell line transfected with the cloned cDNA for human leukocyte 5-lipoxygenase. Two clonal cell lines derived from the transfected cells expressed the enzymatic activity. When incubated with arachidonic acid (100 microM), the major 5-lipoxygenase products of 10,000 X g supernatants from these cells were 5-hydroxyeicosatetraenoic acid (5-HETE), and the nonenzymatic hydrolysis products of leukotriene (LT)A4. The ratio of 5-HETE to LT (between 6:1 and 9:1) was similar to that observed in leukocyte supernatants. Furthermore, incubation of 10,000 X g supernatants from the transfected cells with 5-hydroperoxyeicosatetraenoic acid (5-HPETE) (75 microM) resulted in the synthesis of LTA4 hydrolysis products. Control osteosarcoma cell supernatants produced no 5-HETE or LT from arachidonic acid or 5-HPETE. Maximal activity of the expressed enzyme required Ca2+, ATP, and two cellular stimulatory factors prepared from human leukocytes. Immunoblot analysis of supernatants from the osteosarcoma cell clones revealed an immunoreactive 80,000-dalton band that was indistinguishable from the band observed in leukocyte supernatants. Therefore, the expressed enzyme was functional and exhibited characteristics that were identical to those of human leukocyte 5-lipoxygenase. When intact transfected osteosarcoma cells were challenged with ionophore A 23187, no 5-lipoxygenase products were formed. If arachidonic acid was added along with the ionophore, the cells synthesized 5-HETE and the nonenzymatic hydrolysis products of LTA4. These results verify that the cDNA used to transfect the osteosarcoma cells encodes for 5-lipoxygenase. Furthermore, these studies offer independent evidence that this single protein possesses both 5-lipoxygenase and LTA4 synthase activity, as has been reported previously from enzyme purification data.

Arachidonate 5-Lipoxygenase↗
PubMed1988

Gonadotropin-induced ovulation in a reptile (Anolis carolinensis): histological observations.

Although much is known about morphological changes in the apex of the mammalian ovarian follicle prior to its rupture (ovulation), information about this process in nonmammalian vertebrates is limited to only a few species. We describe here the histological changes in the stigma of the lizard (Anolis carolinensis) ovarian follicle preceding FSH-induced ovulation. Females with a large vitellogenic follicle received two injections, separated by 7 hr, of either porcine FSH (25 micrograms) or saline, and then were sampled at 6, 9, 12, 15, 18, and 24 hr after the first injection. Thus, all but the 6-hr group received two injections. By 12 hr, about half of the FSH-treated females had ovulated, and most had ovulated by 15 hr. In contrast, only 1 of 40 control females ovulated. Large unovulated follicles were fixed and bisected through the circular stigma; one hemisphere was embedded in paraffin and stained with Mallory's trichrome, and the other was embedded in plastic and stained with toluidine blue. FSH treatment produced marked histological changes in the stigma region, as well as alterations in nonstigmal areas of the follicle. The membrana granulosa of control follicles consisted of a single layer of squamous, darkly staining granulosa cells. After FSH treatment, nonstigmal granulosa cells separated slightly, and their nuclei became more clear and assumed an oval shape; in the stigma, these cells became widely separated, with round, light-staining nuclei containing one or two prominent nucleoli. The nonstigmal theca of FSH-treated follicles was similar to that of control follicles except that collagen fibers were more dissociated. In the stigma, collagen fibers were widely dissociated, and the theca swelled, presumably due to accumulation of extracellular fluid. Abundant fluid accumulated in the stigma, especially between the granulosa cells and their basement membrane and between the tunica albuginea and the theca externa. These changes in the lizard stigma are similar to those reported in mammals except that no marked inflammatory response occurs in the lizard stigma. We hypothesize that the Anolis follicle undergoes preovulatory luteinization, and that the stigma exhibits ischemic necrosis before rupture.

Animals↗
PubMed1988

Primary gastric lymphoma. Problems in staging and management.

A retrospective review of 28 patients with primary gastric lymphoma was performed to determine the optimal treatment modality. The presenting signs and symptoms resembled peptic ulcer disease or gastric carcinomas. The majority of the lymphomas were of the diffuse histiocytic subtype. There was a 75 percent resectability rate in those patients operated on. Palliative resection produced a 5 year duration of survival of 28 percent and curative resection, 43 percent. Eighteen patients underwent a subtotal gastrectomy, and a total of 10 patients presented with stage I disease. The longest median duration of survival at last follow-up was 32 months for patients with stage IB disease compared with a median duration of survival of 8 months for those with stage III disease. Adjuvant radiotherapy and chemotherapy may improve survival after a curative resection is performed if there is serosal penetration or nodal involvement.

Adult↗
PubMed1988

Cloning of the cDNA for human 5-lipoxygenase.

The enzyme 5-lipoxygenase (5-LO) catalyzes the first two reactions in the pathway leading to the formation of leukotrienes from arachidonic acid. Leukotrienes are potent arachidonic acid metabolites possessing biological activities that suggest a role in the pathophysiology of allergic and inflammatory diseases. To obtain structural information about 5-LO for use in developing anti-inflammatory chemotherapeutic agents, the enzyme was purified from human polymorphonuclear leukocytes and the amino acid sequences were determined for several cyanogen bromide-derived peptides. A cDNA clone encoding a 674-amino acid protein containing all of the derived peptide sequences was isolated from a dimethyl sulfoxide differentiated HL60 cell cDNA library. The mRNA encoding 5-LO was detected only in differentiated HL60 cells and not in the undifferentiated cell line, indicating that the expression of 5-LO in this cell line is transcriptionally regulated. In addition, the human protein displays some amino acid sequence homology with several lipases and significant homology with the partial sequences of soybean and reticulocyte lipoxygenases. Thus, 5-LO appears to be a member of a larger family of related enzymes.

Amino Acid Sequence↗
PubMed1988

Evidence for the regulation of fatty acid utilization in human sperm by docosahexaenoic acid.

The effects of stearic (18:0), linolenic (18:3), and docosahexaenoic (22:6) acids on palmitoyl coenzyme A (CoA) formation by a long-chain fatty acid:CoASH ligase (adenosine monophosphate) (E. C. 6.2.1.3-enriched fraction from human spermatozoa were studied. Both 18:0 and 18:3 were competitive inhibitors for palmitic (16:0) acid activation with Kis of 17.7 and 5.7 microM, respectively. In contrast, 22:6 was a noncompetitive inhibitor demonstrating a Ki of 9.5 microM. These data coupled with previous studies support the conclusion that 16:0, 18:0, and 18:3 and other saturated and unsaturated fatty acids are activated by the same ligase enzyme in sperm. Although the kinetics and interactions of 22:6 are unique compared to the other fatty acids found in sperm phospholipids, we cannot discern from our data if it is activated by a separate enzyme. We propose that 22:6, or a metabolite of 22:6, may regulate free fatty acid utilization in human sperm and that this hypothesis may provide an enzymatic explanation for the changes observed in phospholipid-bound fatty acids during the epididymal maturation of sperm.

Coenzyme A Ligases↗
PubMed1988

Splenectomy in hematologic disorders. The ever-changing indications.

A comparison between a series of splenectomies performed at the University of Virginia Medical Center for hematologic disorders between 1946 and 1962 (Series I) and 1963 and 1982 (Series II) is presented. Four hundred splenectomies (20 per year) were performed between 1963 and 1982 compared with 94 (5.5 per year) between 1946 and 1962. Also noted in Series II was a sharp decline in the number performed each year between 1974 and 1983. The major factor responsible for these observations was the evolution of the staging laparotomy for malignant lymphomas, particularly Hodgkin's disease, and the decline in the average annual incidence of staging laparotomies since 1974. Staging laparotomy currently is rarely done for non-Hodgkin's lymphomas. Also contributing to the changes noted was an increase in the total number but subsequent fall in the annual incidence of splenectomy for hereditary spherocytosis, idiopathic hypersplenism, and myeloproliferative disorders in Series II. The average number of splenectomies for idiopathic thrombocytopenic purpura increased from 1.1 per year in Series I to 3.6 per year in Series II; the annual incidence during the study period of Series II, however, remained constant. The total number of splenectomies for hairy cell leukemia and Felty's syndrome increased from zero in Series I to 12 and 17, respectively, in Series II, whereas the number of miscellaneous reasons dropped from 29 (1.7 per year) in Series I to 15 (0.75 per year) in Series II. The mortality rate in Series I was 6.3% compared with 4.0% in Series II. No deaths occurred in Series II after 1979. Indications for splenectomy in Series II were for diagnostic purposes in 3.2%, therapeutic in 56.5%, staging in 39.5%, and restaging in 0.8%. Accessory spleens were found in 49 (12.5%) in Series II.

Hematologic Diseases↗
PubMed1988

Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin.

Sex hormone-binding globulin (SHBG) production in humans has been thought to be stimulated by estrogens and thyroid hormone and inhibited by androgens. However, recent data indicate that SHBG production in vitro is stimulated by both androgens and estrogens. This study was designed to determine what other hormonal factors regulate SHBG production. Since hyperinsulinemia and hyperprolactinemia both occur in disease states in which low serum SHBG levels are found, the effects of insulin and PRL were compared to and/or studied in combination with estradiol (E2), T4, and testosterone (T) in a human hepatoma cell line (Hep G2). Hep G2 cells were grown to near confluence in medium including 10% fetal calf serum, and then 72-h experimental incubations were carried out which used only fetal calf serum-free medium. Compared to control incubations, both insulin (10(-8) mol/L) and PRL (10(-8) mol/L) decreased SHBG production from 65.0 +/- 0.6 (+/- SE) to 46.8 +/- 1.1 and 46.8 +/- 1.2 nmol/10(6) cells, respectively (P less than 0.01). Insulin also inhibited both E2 and T4-stimulated SHBG production. T stimulated SHBG production to the same degree as E2. Finally, both E2 and insulin significantly increased cell number, an important consideration when expressing the effect of a hormone on SHBG production in cultured cells. We conclude that insulin and PRL inhibit SHBG production and confirm that T4, T, and E2 stimulate SHBG production in vitro. These findings suggest that insulin and PRL may be important factors in the regulation of SHBG production in vivo.

Carcinoma, Hepatocellular↗
PubMed1988

Pulmonary granuloma formation in murine toxocariasis: transfer of granulomatous hypersensitivity using bronchoalveolar lavage cells.

A major drawback to studying granuloma formation in murine toxocariasis is the ability of the second-stage larva of Toxocara canis to escape from a developing granuloma, migrate elsewhere, and initiate granuloma formation anew. In an attempt to circumvent this difficulty, 2 different T. canis-derived antigenic preparations were covalently attached to Sepharose 4B beads and embolized into the microvasculature of the lungs of CBA/J mice that had been infected 10 days previously with 25 T. canis ova. Both T. canis egg extract (TEE) and T. canis exoantigens (TEX) were able to elicit antigen-specific granulomas 6 days postembolization as determined by both histologic and morphologic criteria. Histologically, the eosinophil-rich granulomas forming around antigen-coated beads embolized into infected mice resembled the developing granuloma previously described forming around the second-stage larva. Attempts to transfer granulomatous reactivity in this model using either immune spleen cells or immune serum were unsuccessful. Successful transfer of granulomatous hypersensitivity was achieved using cells obtained by bronchoalveolar lavage of previously infected mice. The results suggest the feasibility of using this embolic model of granuloma formation in murine toxocariasis.

Animals↗
PubMed1987

Seasonal changes in the effects of arginine vasotocin and stretch on Anolis uterine contractions in vitro.

We determined the effects of acute stretch on spontaneous and arginine vasotocin (AVT)-driven contractions of the Anolis carolinensis uterus in vitro. Whole uteri from reproductively inactive females (October) were placed in a bath of oxygenated 32 degrees C Anolis "Ringer's." Two initial tensions were utilized, 1.5 g or 15 g, the latter being an estimate of the tension on the wall of a uterine compartment. Uteri were then exposed to either saline or AVT (50 ng/ml), and spontaneous or AVT-driven contractions were recorded for 20 min with the use of a strain gauge and physiograph. A similar experiment was performed on uteri from reproductively active females in the summer (June). Our results indicate that the effects of acute stretch and AVT on uterine contractility were qualitatively similar in summer and fall. That is, AVT induced a tonic contraction; stretch decreased the duration of the tonic contraction; the saline-treated uteri exhibited spontaneous rhythmic contractions; AVT increased the amplitude of the rhythmic contractions, but only at the lower tension; there were no effects of AVT on the timing (contraction interval, duration, rest interval) of the rhythmic contractions; and stretch increased the frequency of the rhythmic contractions. Season greatly influenced the magnitude of these contractile phenomena. Uteri tested during the breeding season exhibited greater distensibility, an increase in the amplitude and duration of the AVT-driven tonic contraction, and an increase in the frequency of both spontaneous and AVT-driven rhythmic contractions because of a decrease in both contraction duration and rest interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Conservation of delta-crystallin gene structure between ducks and chickens.

A cloned chicken delta-crystallin cDNA was used to identify two putative delta-crystallin genes in the duck by Southern blot hybridization. A DNA fragment containing most of one of these genes was isolated from a library made in bacteriophage lambda Charon 28A containing genomic DNA from 14-day-old embryonic ducks. Electron microscopy, partial gene sequencing, primer extension analysis using duck mRNA, and comparison with the well-characterized chicken delta-crystallin genes suggest that our cloned duck delta-crystallin gene, like the chicken delta-crystallin genes, is 8-10 kb long and contains 17 exons. Hybridization and sequencing data show great similarity between the homologous 5' untranslated and coding exons of the duck and chicken delta-crystallin genes. Overall, the homologous introns also appear to have approximately 30% sequence similarity, and have been subject to deletion/insertion events. Our partial characterization of duck delta-crystallin gene sequences suggests that this avian and reptilian crystallin family has been conserved during evolution, as have the other crystallin gene families that are expressed in the eye lens.

Animals↗
PubMed1987

Expression and secretion in yeast of a 400-kDa envelope glycoprotein derived from Epstein-Barr virus.

The major envelope glycoprotein (gp350) of Epstein-Barr virus has been expressed and secreted in the yeast Saccharomyces cerevisiae as a 400-kDa glycoprotein. This is the first example of the secretion of such a large, heavily glycosylated heterologous protein in yeast. Since gp350 proved highly toxic to S. cerevisiae, initial cellular growth required repression of the expression of gp350. Using temperature- or galactose-inducible promoters, cells could be grown and the expression of gp350 then induced. After induction, the glycoprotein accumulated both intracellularly as well as in the culture medium. Only the most heavily glycosylated form was secreted, suggesting a role for N-linked glycans in directing secretion. The extent of O-linked glycosylation of the yeast-derived protein was similar to that of the mature viral gp350. N-linked glycosylation varied slightly depending upon culture conditions and host strain used and was more extensive than that associated with the mature viral gp350. Although there is no evidence that more than a single mRNA for the glycoprotein was expressed from the recombinant plasmid, variously sized glycoproteins accumulated in yeast at early stages after induction, probably reflecting intermediates in glycosylation. The yeast-derived glycoproteins reacted with animal and human polyclonal antibodies to gp350 as well as with a neutralizing murine monoclonal antibody to gp350, suggesting that this glycoprotein retains several epitopes of the native glycoprotein.

Cloning, Molecular↗
PubMed1987

Bilateral renal artery embolism: a diagnostic and therapeutic problem.

A case of bilateral renal artery embolism in a patient occurring after coronary artery bypass operation is reported, describing the diagnostic techniques and therapeutic aspects of management of this unusual disease. The diagnosis should be suspected in patients with underlying cardiovascular disease who have acute renal failure.

Coronary Artery Bypass↗
PubMed1987

Use of bronchoalveolar lavage to compare local pulmonary immunity with the systemic immune response of Toxocara canis-infected mice.

Following infection of mice with larvae of the canine roundworm Toxocara canis, there is a persistent pneumonitis. Heretofore, nothing was known about the immunologic potential of the cells that constitute this inflammatory exudate. By performing bronchoalveolar lavage (BAL), enough inflammatory cells were obtained to compare the local pulmonary immune response to T. canis infection with the systemic immune response as reflected in the peripheral blood and spleen cells of the same mice. Groups of C57BL/6J female mice were given 100 infective ova and BAL, peripheral blood, and spleen cells collected on days 8, 11, 14, and 17 postinfection. The percentage of eosinophils in the BAL averaged about 80% and was four to five times as great as that in the peripheral blood at all times assayed. Use of concanavalin A (ConA)-elicited lymphocyte blastogenesis to evaluate T-lymphocyte activity revealed that BAL T-cell activity was low on day 8 and peaked on day 11. When the B-cell mitogen lipopolysaccharide was used in the assay, there appeared to be far less BAL cell reactivity compared with BAL T-cell activity. Both B- and T-cell responses of the BAL cells were only a fraction of the responses seen concurrently in spleen cells. Use of Toxocara exoantigens in the blastogenesis assay revealed that Toxocara exoantigens could elicit between 20 and 95% of the ConA response in BAL cells, while in spleen cells Toxocara exoantigens could only elicit 1 to 5% of the ConA response. These results suggest that BAL is a useful method for recovering local inflammatory cells that possess detectable immunologic activity. In the case of pulmonary toxocariasis, eosinophils account for the majority of the cells that are present, with most of the remaining cells being T. canis antigen-specific T lymphocytes.

Animals↗