PubMed Health⌕ Search

Biomedical subjects

C D Jones

Publications and source records attributed to C D Jones.

At least 109 records · Page 6Linked to original sources
PubMed1997

Color Doppler ultrasonographic detection of a vibrating needle system.

The purpose of this study was to compare needle detection using a commercially available vibrating needle system that is used with color Doppler sonography and conventional real-time needle guidance during ultrasonographically guided intervention. Twenty-four paired (48 total) sonographically guided needle placements were performed in 22 patients for fine needle biopsy. Two patients underwent two additional needle placements at later times and, therefore, underwent a total of four needle passes each. Twenty-four of the needles were placed utilizing conventional real-time ultrasonographic guidance, and 24 were guided using a commercially available vibrating needle system. The Color Mark System was compared with standard technique for needle visualization and graded according to ease of needle visualization (improved, no change, or more difficult visualization). This was done for both needle tip and needle shaft visualization. Visualization was graded in both superficial (less than 3 cm deep) and deep structures. Overall needle tip and shaft visualization improved in 14 of 24 cases in superficial tissues and in three of 24 cases in superficial and deep tissues with the Color Mark System. The vibrating needle system also was judged to be somewhat cumbersome when used with a 22 gauge needle, as its weight tended to bend the needle shaft. The needle vibrating system may enhance needle visualization in superficial structures, but with the present design it is of limited use in deep tissues.

Biopsy, Needle↗
PubMed1996

Hepatic ablation using bipolar radiofrequency electrocautery.

RATIONALE AND OBJECTIVES: Percutaneous methods have been used to treat primary and secondary hepatic neoplasms. In the current study, we evaluated the potential of bipolar radiofrequency (RF) electrocautery to increase in vitro liver tissue destruction when compared with monopolar RF electrocautery. METHODS: Two needles (electrodes) were placed into fresh bovine liver tissue for use with bipolar electrocautery. Needle tip exposure was kept constant at 3 cm while other parameters, including treatment time, power (wattage), interneedle distance, and needle tip temperature, were changed. Pathologic and histologic correlation was performed, and tissue necrosis was weighed in grams for individual parameters. RESULTS: There was a minimal threshold of approximately 45 degrees C where tissue coagulation occurred. Tissue coagulation increased the longer treatment went on. Increasing temperature, wattage, or both increased tissue coagulation such that necrosis was too rapid and char formation occurred, which prevented further coagulation. For all wattages and temperatures, there was increasing tissue necrosis with increasing needle separation, until a point at which further needle separation produced less tissue necrosis. Optimizing parameters allowed tissue coagulation of greater than 30 g. CONCLUSION: Bipolar RF electrocautery shows promise for increasing the tissue coagulation in fresh bovine liver compared with the previously described monopolar technique.

Animals↗
PubMed1996

Effects of phototherapy on the production of cytokines by peripheral blood mononuclear cells and on systemic antibody responses in patients with psoriasis.

Exposure to ultraviolet B (UVB) radiation results in the suppression of many cell-mediated immune responses, and recent studies mice and murine cells in vitro suggest a shift from a T-helper 1 (Th1) to a Th2 type of response on irradiation. Active psoriasis is considered to be a Th1-type disorder, chiefly on the basis of the cytokines produced by inflammatory cells in psoriatic lesions. We investigated the effect of phototherapy in patients with psoriasis on the cytokine profile of mitogen-stimulated mononuclear cells from peripheral blood and the concentration of IgG subclasses and IgE in the plasma. Eight patients were irradiated with a broad-band UV source (Sylvania UV6; 280-400 nm) three times a week and another eight with a narrow-band UVB source (Philips TL-01; 311-313 nm). Peripheral blood was collected before therapy started and after 1-4 weeks of therapy. Peripheral blood mononuclear cells were stimulated in vitro with phytohemagglutinin; proliferation was measured by incorporation of tritiated thymidine and culture supernatants assayed for interleukin (IL)-2, -4 and -10 and gamma-interferon (IFN) by enzyme-linked immunosorbent assays. Lymphoproliferation was not consistently affected by 4 weeks of UV6 therapy, and there was also no consistent change in the production of IL-2, IL-10 or gamma-IFN. In contrast, 4 weeks of TL-01 therapy significantly suppressed lymphoproliferative responses. In addition the production of IL-2, IL-10 and gamma-IFN was lowered after 1 week of TL-01 therapy, and this was even more apparent after the treatment had been extended to 4 weeks. IL-4 concentrations were below detectable levels in all the samples throughout the study. The amounts of IgG1, -2, -3 and -4 and IgE in the plasma of the patients did not vary with either of the two phototherapies. Thus, although no evidence was obtained to indicate that UV6 exposures affected T-helper subsets in psoriasis, TL-01 inhibited the activity of both Th1 and Th2 subsets while not altering plasma antibody concentrations.

Adult↗
PubMed1996

Investigating the red shift between in vitro and in vivo urocanic acid photoisomerization action spectra.

Trans-urocanic acid (UCA) is found in the upper layer of the skin and UV irradiation induces its photoisomerization to cis-UCA. Cis-UCA mimics some of the immunosuppressive properties of UV exposure. The wavelength dependence for in vitro photoisomerization of trans-UCA (15 microM) over the spectral range 250 nm-340 nm (10 nm intervals) was determined. The action spectrum revealed that maximal cis-UCA production occurred at 280 nm, which is red-shifted by 10-12 nm from its absorption peak at 268 nm and differs markedly from the reported action spectra for cis-UCA production in mouse skin in vivo, which peaks at 300-310 nm. The reasons for the red shift between the in vitro and in vivo action spectra are not clear. There is limited evidence suggesting that the UV absorption maximum of trans-UCA red shifts from 268 nm in vitro to 310 nm on interaction with stratum corneum proteins in vivo. This phenomenon was investigated by applying trans-UCA (2.5 mg/cm2) in an oil emulsion to isolated human stratum corneum. After incubation at 37 degrees C for 1 h, the absorption spectra of stratum corneum with UCA and with oil only were compared using a Xe arc source and a spectroradiometer. A moderate red shift in trans-UCA absorption from approximately 268 nm to 280 nm was observed. In summary, we suggest that the 10-12 nm red shift between the UCA absorption spectrum peak and the action spectrum peak in vitro may be accounted for by the wavelength dependence of quantum yields reported over the 254-313 nm range. The red shift between the in vitro and in vivo photoisomerization action spectra may result from the 10 to 12 nm red shift in the absorption of UCA in association with stratum corneum proteins, combined with increasing quantum yields over the 254-313 nm range.

Humans↗
PubMed1996

Pelvic abscesses: transvaginal US-guided drainage with the trocar method.

The effectiveness of the trocar technique of catheter placement for transvaginal sonographically guided drainage of pelvic abscess was assessed in seven women who presented with pelvic pain, fever, and presumed pelvic abscess. Endovaginal ultrasound was performed to document fluid collection before drainage. All procedures were performed in less than 1 hour, without complications. Catheters were left in place for 1-3 days. Catheter placement was curative in six of seven patients (86%).

Abscess↗
PubMed1996

LY191704 inhibits type I steroid 5 alpha-reductase in human scalp.

Conversion of testosterone to dihydrotestosterone (DHT) has been demonstrated to be catalyzed by two isoforms of steroid 5 alpha-reductase, designated types I and II. Although several classes of steroid-based inhibitors of the type II isoform have been identified, these agents have not demonstrated highly selective pharmacological activity against human type I 5 alpha-reductase. LY191704 is representative of a series of nonsteroidal agents that have potent [apparent inhibitory constant (Ki) = 11.3 nM] inhibitory activity in human scalp skin homogenates (pH 7.5), a source of type I 5 alpha-reductase. [3H]-DHT production in the presence and absence of LY191704 is consistent with a noncompetitive mode of inhibition. In human prostatic homogenates (pH 5.5), a source of type II 5 alpha-reductase, LY191704 is virtually inactive as an inhibitor [concentration of inhibitor producing 50% inhibition of enzymatic activity (IC50) > 1,000 nM] of [3H]-DHT formation. LY191704 does not inhibit the type I or type II isoforms of rat 5 alpha-reductase, nor does the compound compete for binding to the murine androgen receptor expressed in SF9 cells using a baculo virus expression system. The benzoquinolinones, as exemplified by LY191704, possess exquisite pharmacological selectivity and provide a tool to understand the role of human type I 5 alpha-reductase in normal and pathophysiological states. These agents may also find clinical utility in treating androgen-dependent dermatological conditions.

5-alpha Reductase Inhibitors↗
PubMed1995

Raloxifene (LY156758) produces antimetastatic responses and extends survival in the PAIII rat prostatic adenocarcinoma model.

The benzothiophene antiestrogen, raloxifene (LY156758), has selective estrogen pharmacological antagonist activity in rats. The PAIII rat prostatic adenocarcinoma model was used to evaluate the effects of this agent on the lymphatic and pulmonary metastasis and survival in tumor-bearing male Lobund-Wistar (LW) rats. Raloxifene was inactive against colony formation of PAIII cells in vitro. Similarly, following subcutaneous (s.c.) implantation of 10(6) PAIII cells in the tail, s.c. administration of raloxifene (2.0, 10.0, or 20.0 mg/kg/day) for 30 days failed to demonstrate cytoreductive activity against primary tumor growth in the tail. However, in these same animals, raloxifene administration produced significant (P < 0.05) inhibition of PAIII metastasis from the primary tumor in the tail to the gluteal and iliac lymph nodes (maximal responses = 89% and 81% from control values, respectively). PAIII metastasis to the lungs was significantly inhibited by raloxifene treatment. Numbers of pulmonary foci in PAIII-bearing rats were significantly (P < 0.05) reduced by raloxifene administration in a dose-related manner (maximal reduction = 97% from control values). In these animals, maximal regression of 20% for ventral prostate and 21% for seminal vesicle were also seen after raloxifene administration (P < 0.05 for both). Coadministration of E2B and raloxifene had no consistent antagonistic effect upon the antitumor responses produced by raloxifene. Raloxifene (40.0 mg/kg/day for 28 days) produced marked decreases in PAIII metastasis in the lymphatic and pulmonary components. Continued administration of the compound produced significant (P < 0.05) extension of survival of PAIII-bearing rats. Further studies are needed to define the maximal antitumor efficacy and the mechanism of action of raloxifene in urogenital solid tumor animal models. These data support the contention that raloxifene represents a class of active antimetastatic agents with potential efficacy in the treatment of hormone-insensitive human prostatic cancer.

Adenocarcinoma↗
PubMed1995

The popliteus as a retractor of the lateral meniscus of the knee.

Because of inconsistencies in the literature regarding popliteus and its relation to the lateral meniscus, it was decided to investigate the influence on the behavior of the lateral meniscus of contraction of the popliteus muscle via arthroscopy. A series of 50 knees from 44 patients who underwent elective arthroscopic surgery were examined. During arthroscopy, popliteus was stimulated to contract using surface electrodes. Any resultant meniscal retraction was observed and recorded. Thirty-one knees showed such retraction, and no retraction was observed in the remaining 19 knees. The clinical implications of this study are limited, but the results may support a number of proposed theories. It may be concluded that in a population exhibiting normal, intact lateral menisci, popliteus variably acts as a retractor of the lateral meniscus.

Adolescent↗
PubMed1995

Immunomodulation at the initiation of phototherapy and photochemotherapy.

The numbers and function of circulating lymphocyte subsets are within normal ranges in patients with psoriasis and are not affected by 4 weeks of ultraviolet (UV) therapy, except for a suppression in natural killer (NK) cell activity. However, it is possible that immunomodulation might occur at the initiation of phototherapy with a return to control values on more prolonged UV exposure. Thus, in this study the responses of 15 patients with chronic plaque psoriasis undergoing broad-band UVB therapy, 10 narrow-band (311-313 nm) UVB therapy and 10 PUVA therapy were compared. In each case, samples were taken immediately before starting treatment and 1 week later. Broad-band UVB and PUVA therapy had no effect on NK activity, but a significant reduction was found in the group receiving narrow-band UVB. In vitro lymphoproliferative responses to mitogens and to herpes simplex virus antigens did not alter with therapy, except there was a significant increase in mitogen responses (at optimal mitogen concentrations only) in the narrow-band UVB group. Generally no alterations in overall percentages of circulating mononuclear cells were found in any group. Samples were taken from the epidermis of the forearm and back of the patients receiving narrow-band UVB for the quantification of urocanic acid (UCA) isomers. The total UCA concentration remained unchanged after 1 week of therapy, while the percentage of cis-UCA increased significantly at both sites in the majority of patients. However, this rise did not correlate with the decrease in NK cell activity and the two parameters may not be related causally.

Adult↗
PubMed1994

The in vitro anti-hepatitis B virus activity of FIAU [1-(2'-deoxy-2'-fluoro-1-beta-D-arabinofuranosyl-5-iodo)uracil] is selective, reversible, and determined, at least in part, by the host cell.

A human hepatoblastoma cell line was stably transfected with a head-to-tail dimer of the Hepatitis B virus (HBV), subtype adw, genome to generate a cell line which produces HBV. FIAU [1-(2'-deoxy-2'-fluoro-1-beta-D-arabinofuranosyl-5-iodo)uracil] inhibited viral replication in these cells with an IC50 of 0.90 microM, as determined by PCR analysis of extracellular Dane particle DNA, and displayed a 50% cytotoxic concentration (TC50) of 344.3 microM, as determined using the MTT assay. The selectivity index of FIAU (TC50/IC50) was 382.6. In cells incubated for 10 days with FIAU (100 microM) and then incubated with drug-free media with daily media changes for 7 days, viral DNA replication was markedly inhibited but resumed within 24 h after drug removal, demonstrating that the in vitro anti-HBV activity of FIAU is reversible. Both the antiviral activity and cytotoxicity of FIAU were reversed by the addition of equimolar to 10-fold excess molar concentrations of thymidine. The de-iodinated metabolite of FIAU, FAU, had only marginal anti-HBV activity at 100 microM, indicating that this metabolite does not contribute significantly to the activity of FIAU. The examination of intracellular viral DNA replicative intermediates revealed that FIAU was 2000-fold more active against duck HBV DNA replication in human hepatoma cells (IC50 = 0.075 microM) than against this same virus in chicken liver cells (IC50 = 156 microM). FIAU was anabolized to a 25-fold greater extent in human hepatoma cells than in chicken cells, indicating that the anti-HBV activity of this nucleoside analog is dependent, in part, on its phosphorylation by the host cell.

Antiviral Agents↗
PubMed1994

Sensitive and specific radioimmunoassay for fialuridine: initial assessment of pharmacokinetics after single oral doses to healthy volunteers.

Fialuridine (FIAU) is a halogen-substituted analog of thymidine that was undergoing clinical investigation as a drug for the treatment of chronic hepatitis B viral infection. However, clinical trials of FIAU were terminated after adverse events occurred following chronic oral administration. Prior to the termination of clinical trials, a sensitive assay was needed for the measurement of FIAU because of the anticipated low dose administered to patients. We therefore undertook the development of a radioimmunoassay (RIA). A specific antiserum was raised in rabbits following immunization with a 5'-O-hemisuccinate analog of FIAU coupled to keyhole limpet hemocyanin. Radiolabeled FIAU was synthesized by a destannylation procedure by using sodium [125I]iodide. We developed a competitive-binding procedure and used precipitation with polyethylene glycol as the method for separating the bound and free forms of FIAU. The RIA is sensitive (0.2 ng/ml), specific (negligible interference from known metabolites and endogenous nucleosides), and reproducible (interassay coefficients of variation range from 5 to 19.7% for serum controls). We used the RIA to assess the pharmacokinetics of FIAU in healthy adult volunteers following administration of a single 5-mg oral dose. The sensitivity of the RIA permitted the detection of a prolonged elimination phase for FIAU in healthy volunteers and dogs, with mean elimination half-lives of 29.3 and 35.3 h, respectively. We conclude the RIA is a valid method for the quantification of FIAU in biological fluids.

Administration, Oral↗
PubMed1993

LY191704: a selective, nonsteroidal inhibitor of human steroid 5 alpha-reductase type 1.

Androgens, in particular dihydrotestosterone (DHT), play a key role in differentiation, growth, and maintenance of the mammalian prostate. Production of DHT from testosterone is catalyzed by two distinct membrane-bound steroid 5 alpha-reductase [5 alpha-reductase; 3-oxo-5 alpha-steroid delta 4-dehydrogenase; 3-oxo-5 alpha-steroid:(acceptor) delta 4-oxidoreductase, EC 1.3.99.5] isozymes designated types 1 and 2. Benign prostatic hyperplasia (BPH), a disease that occurs almost universally in males, is characterized by obstructive and irritative urinary voiding symptoms and has been associated with an overproduction of DHT. Recently, steroidal inhibitors of 5 alpha-reductase type 2 have been used successfully for treatment of BPH. Described here is a nonsteroidal inhibitor of 5 alpha-reductase type 1, LY191704 (8-chloro-4-methyl-1,2,3,4,4a,5,6,10b-octaahydro-benzo[f]quinol in-3(2H)-one). This compound was identified based on its capacity to inhibit 5 alpha-reductase activity in a human genital skin fibroblast cell line (Hs68). Surprisingly, LY191704 is inactive when tested in freshly isolated prostate cells obtained from subjects with BPH, whereas previously described 4-azasteroids are active. LY191704 is, however, a potent inhibitor of the 5 alpha-reductase activity of BPH cells that have been maintained in culture. Analysis of human and rat 5 alpha-reductases expressed from transfected cDNAs in simian COS cells indicates that LY191704 is a specific noncompetitive inhibitor of the human 5 alpha-reductase type 1. Taken together, the results suggest that prostate cells have the capacity to express both 5 alpha-reductase isozymes and that LY191704 may be useful in treatment of human endocrine disorders associated with overproduction of DHT by 5 alpha-reductase type 1.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1993

Endocrine and antiprostatic effects of raloxifene (LY156758) in the male rat.

The benzothiophene anti-estrogen, raloxifene [LY156758; (6-hydroxy-2-(4-hydroxyphenyl) benzo(b)thien-3-yl)(4-(2-1-piperidinyl)ethoxy)phenyl methanone hydrochloride] has selective estrogen pharmacological antagonist activity in female rats. The present studies were done in the male rat to assess activity of raloxifene related to inhibition of prostatic growth and effects on the hypothalamic-pituitary-gonadal axis. Raloxifene did not compete for binding of the androgen, [3H]-methyltrienolone (R1881) in cytosolic extracts of ventral prostate. Similarly, the compound did not inhibit prostatic 5 alpha-reductase or testicular 17 alpha-hydroxy/C17,20-lyase activities. Raloxifene had no effect on the ventral prostatic uptake of [3H]-R1881 in vivo. Administration of estradiol to castrated male rats stimulated fourfold increases of in vitro ventral prostatic binding of [3H]-R1881. Raloxifene was devoid of agonist activity in castrated animals, because the compound had no stimulatory effect on prostatic androgen receptor binding activity. When raloxifene was coadministered with estradiol, the compound markedly antagonized the estrogen-induced increase of prostatic [3H]-R1881 binding, confirming its antiestrogenic properties in male rats. Serum prolactin was also elevated significantly (P < 0.05) with a single injection of raloxifene (20.0 mg/kg). In these same animals, serum FSH was significantly (P < 0.05) decreased by one dose (10.0 mg/kg) of the compound. Luteinizing hormone levels in castrated male rats were unaffected by raloxifene administration. Raloxifene treatment of castrated males significantly (P < 0.05) antagonized the stimulatory response of the ventral prostate (VP) to exogenous androgens in a dose-dependent manner. Raloxifene treatment of intact male rats for 14 and 28 days produced significant (P < 0.05) dose-dependent regression of the VP and seminal vesicles (SV). The VP regressive responses to raloxifene were associated with a decline in serum testosterone levels. Histological analysis of the VPs in raloxifene-treated rats was consistent with an androgen-deprived state. These findings support the contention that raloxifene is a pure estrogen antagonist and a physiological antagonist of androgen action in male rats. These pharmacological properties provide support for further structure-activity and mechanistic investigations with benzothiophenes in the medical management of prostatic neoplasia.

Aldehyde-Lyases↗
PubMed1993

Thiopurine methyltransferase activity in a sample population of black subjects in Florida.

Thiopurine methyltransferase (TPMT), is an enzyme detected in the human red blood cell that catalyzes the S-methylation of thiopurine drugs and is known to exist as a genetic polymorphism in white subjects. Investigations in this laboratory of red blood cell TPMT showed interethnic differences also existed in North American black subjects. A sample group of black subjects in Florida had a mean activity of 8.64 +/- 3.47 U/ml red blood cells and an antimode of 6.5 units, which represented values significantly lower than those obtained for both the mean activity and the antimode in other populations. The findings of this study suggest the possibility that TPMT activity may be under genetic control in North American black subjects and that this ethnic group may be at greater risk of experiencing thiopurine-induced toxicity caused by the lower overall mean activity of the enzyme.

Adolescent↗
PubMed1992

Antiestrogens. 3. Estrogen receptor affinities and antiproliferative effects in MCF-7 cells of phenolic analogues of trioxifene, [3,4-dihydro-2-(4- methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]- phenyl]methanone.

Benzothiophenes 3 and 4, derived from the acrylophenone antiestrogen trioxifene (2), are characterized by high estrogen receptor (ER) affinity and low residual estrogenicity compared to tamoxifen (1a). In order to characterize further the growth suppression mechanism for these structural types we have prepared structural variants of 2 bearing hydroxy groups positioned to maximize ER affinity. Thus, dihydronaphthalenes 5 and 6 and benzofluorenes 7 and 8 were prepared and studied in MCF-7 human breast cancer cells, in comparison with 3 and 4. All compounds were powerful suppressants of cell growth, with 50% inhibition ranging from 4.5 to 160 nM. Greatest potency was seen with diphenols 6 and 8. These compounds had intracellular ER affinities ranging from 0.2 to 4.1% of that of estradiol, suggestive of a potential for partial agonist effects. Simultaneous exposure of cells to 0.1 microM concentrations of estradiol and 3 or 4 did not affect the degree of growth inhibition seen with 0.1 microM 3 or 4 alone. Partial reversal of inhibition occurred when 0.1 microM 5-8 were each accompanied by 0.1 microM estradiol. Under these conditions complete reversal of growth inhibition has been found with 1a, 1b, and other triarylethylenes. Calmodulin, a putative target for triarylethylenes, and which is antagonized by 1a, was shown to interact weakly with 7 and 8 and not at all with 3-6. These results suggest that MCF-7 cell growth suppression by 3-8 may be due to interaction with unidentified receptors besides ER and extend earlier findings indicating that events occurring after interaction of these compounds with ER differ from those of triarylethylene antiestrogens.

Antineoplastic Agents↗