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Biomedical subjects

T J Collins

Publications and source records attributed to T J Collins.

At least 73 records · Page 4Linked to original sources
PubMed1993

Percutaneous angioscopy of saphenous vein coronary bypass grafts.

OBJECTIVES: We compared the results of percutaneous angioscopy and angiography for detecting critical elements of surface lesion morphology in 21 patients undergoing balloon angioplasty of saphenous vein coronary bypass grafts. BACKGROUND: Angiography remains the standard for diagnosing and treating intravascular pathology associated with atherosclerotic coronary artery disease. It has been demonstrated that coronary angioscopy is more sensitive for identifying more complex atherosclerotic plaques and intracoronary thrombi in native coronary arteries. METHODS: Angioscopy and angiography were performed before and after angioplasty of "culprit lesions" in bypass grafts. All but one of the patients had unstable angina. The mean age of the saphenous vein coronary bypass grafts was 10.1 +/- 2.4 years (range 5 to 15). RESULTS: Restenosis at a prior angioplasty site was present in seven patients. Intravascular thrombi were seen by angioscopy in 15 (71%) of 21 versus 4 (19%) of 21 grafts by angiography (p < 0.001). Dissection was identified by angioscopy in 14 (66%) of 21 versus 2 (9.5%) of 21 grafts by angiography (p < 0.01). The presence of friable plaque lining the lumen surface of the vein graft was detected by angioscopy in 11 (52%) of 21 versus 4 (19%) of 21 grafts by angiography (p < 0.05). There was no correlation between age of the bypass graft and the finding of friable plaque. CONCLUSIONS: We conclude that angioscopy is superior to angiography for detecting complex lesion morphology in bypass grafts and that the presence of friable plaque does not preclude an uncomplicated angioplasty procedure.

Aged↗
PubMed1993

In vitro DNA damage and mutations induced by a macrocyclic tetraamide chromium(V) complex: implications for the role of Cr(V) peptide complexes in chromium-induced cancers.

Electron paramagnetic resonance and electronic absorption spectroscopies have shown that unlike the bidentate Cr(V) complex [Cr(ehba)2O]- (ehba = 2-hydroxy-2-ethylbutanoato(2-)), I, the macrocyclic tetradentate complex, [Cr (mampa-dcb)(O)]- (mampa-dcb = 5,6-(4,5-dichlorobenzo)-3,8,11,13-tetraoxo-2,2,9,9-tetrameth yl-12,12-diethyl-1, 4,7,10-tetraazacyclotridecane), II, is substitutionally inert. Low levels of DNA strand cleavage were observed after treatment with II under physiological conditions (50 mM sodium phosphate, pH 7.4, 37 degrees C) at concentrations as high as 2 mM for periods as long as 2 days. II also induces a lower number of revertants in mutation assays with Salmonella typhimurium TA100 than I when identical Cr concentrations are applied. The slopes of the linear portion of the dose-response curves are parallel, however, indicating that the mutagenicity of II is comparable to I. II is stable toward ligand exchange, reduction and disproportionation in the mutagenicity test medium and also in the presence of bacteria and the common cell reductant, glutathione. This indicates that ligand exchange with DNA and/or reduction to Cr(IV) are not responsible for the mutagenicity of II (unlike I). It is believed that II reversibly but weakly intercalates with DNA placing the Cr(V) center in close proximity for hydrogen atom abstraction or oxo-transfer reactions to ensure. This tetraamide complex is a good structural and biomimetic model for non-sulfur-containing Cr(V) peptide species that may form in vivo from reactions of Cr(VI) with peptides. Hence, it is likely to be relevant to understanding one possible mechanism by which Cr(VI) causes cancer.

Chromium↗
PubMed1993

Percutaneous coronary angioscopy: applications in interventional cardiology.

We performed percutaneous coronary angioscopy in 35 patients to study the surface morphology of coronary artery lesions. Twenty-five patients had angioscopy performed in conjunction with PTCA, including 20 patients with de novo lesions (16 patients with unstable angina, four patients with stable angina), and five patients with restenosis lesions. Ten cardiac transplant patients had angioscopy performed in conjunction with annual follow-up angiography in attempt to identify accelerated atherosclerotic lesions. There were no complications of angioscopy in any patient. There were no intracoronary thrombi seen either by angiography or angioscopy in the stable angina patients. In the unstable angina group, angiography identified thrombus in 2 out of 16 (12.5%) versus 15 out of 16 (94%) (P less than 0.001) with angioscopy. Following angioplasty, dissections were seen angiographically in 7 out of 16 (44%) of patients versus 16 of 16 (100%) of the patients by angioscopy (P less than 0.01). Restenosis lesions were characterized by a white, fibrous appearance instead of the usual yellow color of primary atherosclerotic lesions. In the ten cardiac transplant patients, angioscopy appeared to be more sensitive than angiography for the detection of atherosclerosis. Yellow (atherosclerotic) and white (fibrotic) plaques were seen in the transplant patients, which often were not detected by angiography. In summary, angioscopy is an excellent tool for visualizing the surface morphology of coronary artery lesions. The clinical indications for angioscopy remain undefined at present.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1992

The occurrence of O-acylation during biotinylation of gonadotropin-releasing hormone and analogs. Evidence for a reactive serine.

Gonadotropin-releasing hormone (GnRH) and two of its analogs ([D-Lys6]GnRH and des-Gly10-[D-Trp6]-GnRH) were reacted with sulfonated N-hydroxysuccinimide esters of biotin that have been reported to react specifically with primary amino groups. Fractionation by reversed-phase high performance liquid chromatography demonstrated the occurrence of multiple biotinylated derivatives for each reacted peptide. These results were unexpected since GnRH and des-Gly10-[D-Trp6]GnRH contained no reactive amino groups and [D-Lys6]GnRH had only one. Reaction of the biotinylated derivatives with hydroxylamine indicated that significant O-biotinylation had occurred. Mass spectrometric analyses established the stoichiometry of biotinylation and confirmed that substantial O-biotinylation of residue Ser4, and to a minor extent Tyr5, of GnRH and the two analogs had occurred. In contrast, the biotinylation of selected peptides unrelated to GnRH under identical reaction conditions indicated no significant evidence of O-acylation of seryl residues. Strikingly, biotinylation of GnRH under denaturing conditions largely abolished O-acylation, indicating that the observed O-biotinylation was dependent on peptide conformation. All the O-biotinylated derivatives displayed significantly reduced bioactivity. Taken together, these results give strong evidence that the Ser4 hydroxyl of GnRH has a significantly elevated intrinsic reactivity, which raises new questions concerning its putative role in the conformation and mode of action of the hormone. These results also demonstrate for the first time that the N-hydroxysuccinimide-biotin esters are capable of significant O-acylation and may be generally useful reagents for detecting highly reactive hydroxyamino acid residues.

Acylation↗
PubMed1992

Transforming growth factor-alpha acts as an autocrine growth factor in ovarian carcinoma cell lines.

The potential of transforming growth factor-alpha (TGF-alpha) to function as an autocrine growth factor was evaluated in numerous ovarian carcinoma cell lines. All 17 lines which were examined expressed the epidermal growth factor receptor and 16 cell lines, in addition, concomitantly secreted TGF-alpha. Radioimmunoassay of processed serum-free-conditioned medium indicated TGF-alpha concentrations ranging from 16 to 197 pg/ml, or 1.5 to 95 ng/10(8) cells. 125I-TGF-alpha bound to a single class of high-affinity-binding sites on the surface of the cells. The dissociation constant for the 125I-TGF-alpha/epidermal growth factor receptor complex ranged from 0.21 to 5.3 nM with receptor numbers from 3,500 to 96,000/cell, depending upon the cell line. The growth of 8 ovarian cell lines was stimulated in a dose-dependent manner when grown in the presence of exogenous TGF-alpha. Growth in 4 of 5 cell lines capable of serum-free propagation was inhibited from 28 to 56% when cultured in medium containing a TGF-alpha-neutralizing monoclonal antibody. These results support the view that TGF-alpha is an autocrine growth factor for cell lines derived from ovarian cancers of epithelial origin and suggest a potential role for TGF-alpha in the pathogenesis or progression of the disease.

Cell Division↗
PubMed1992

Ambiguous coronary angiography: clinical utility of intravascular ultrasound.

We report the use of intravascular ultrasound (IVUS) in situations where angiography was ambiguous or uncertain in assessing the significance of coronary stenoses. The indications for performing intravascular ultrasound were 1) angiographic findings did not correlate with the clinical presentation (n = 5) and 2) the lesion was not seen well by angiography because of overlapping vessels at the site of suspected stenosis (n = 3). We studied eight lesions in seven patients. Six nonobstructive stenoses on angiography were shown by IVUS to be significant. In two patients, stenoses were thought to be significant on angiography, but, due to overlapping of the vessels, there was doubt regarding the severity of the narrowing. In these two patients, IVUS clearly showed that the lesions were nonobstructive. As seen from the above results, angiography underestimated 6/8 stenoses and overestimated in 2/8 stenoses when compared to IVUS. We conclude that IVUS can be used to clarify ambiguous angiographic findings which can have a major impact on the clinical decision making.

Aged↗
PubMed1992

Intracoronary thrombus: chronic urokinase infusion and evaluation with intravascular ultrasound.

Percutaneous revascularization of coronary arteries with intraluminal thrombi is a clinical problem. We report a patient in whom we administered prolonged infusion of intracoronary urokinase and then assessed the stenosis with intravascular ultrasound before and after atherectomy. We found both angiography and intravascular ultrasound to be misleading in determining the presence of residual thrombus after thrombolysis.

Adult↗
PubMed1992

DNA synthesis in nuclei isolated from Daudi B cells: a model to study the antiproliferative mechanisms of interferon-alpha.

To study the antiproliferative response of B cells to interferon-alpha (IFN-alpha) at the molecular level, we developed a cell-free system to assess DNA synthesis in nuclei isolated from IFN-sensitive Daudi B lymphoblastoid cells. [3H]dTTP incorporation in isolated nuclei was shown to be representative of replicative DNA synthesis by evidence that (i) incorporation was dependent on ATP and all four nucleoside precursors, (ii) incorporation was inhibited greater than 97% by aphidicolin, a specific inhibitor of DNA polymerase alpha and delta, and (iii) the DNase I-sensitive product banded in neutral CsCl at a density indicative of replicative DNA. This cell-free model was used in conjunction with flow cytometric cell cycle analysis to determine the effect of IFN-alpha on DNA synthesis in Daudi cells. The addition of IFN-alpha to an IFN-growth sensitive Daudi subclone in G0/early G1 inhibited the initiation of DNA synthesis, assessed in isolated nuclei, and prevented the progression of cells into S phase. IFN-alpha failed to inhibit DNA synthesis or cell cycle progression when added to IFN-sensitive Daudi cells in late G1/early S phase or to an IFN-resistant Daudi subclone. These studies suggest that IFN-alpha inhibits DNA replication and cellular proliferation in Daudi B cells by interfering with G1 cell cycle events.

Cell Division↗
PubMed1992

Differential effects of two alleles of the dy locus on the pituitary-testicular axis of mice.

Testicular function was studied in vivo and in vitro in adult male dy/dy and dy2J/dy2J dystrophic mice. The results demonstrate that testicular function in dy/dy mice is more affected. The basal levels of pituitary hormones measured were normal in dystrophic mice, except for the presence of hyperprolactinemia in dy/dy mice. In dy/dy mice testicular weight was diminished and a deficient transduction of the gonadotropic signal is present in vivo, accompanied by reduced efficiency of 17-hydroxylase and 17-hydroxysteroid dehydrogenase. In dy2J/dy2J mice the signal transduction is normal and the reduction in enzyme efficiency is limited to 17-hydroxysteroid dehydrogenase. The in vitro HCG-induced increases in production of testosterone (T) and estradiol (E2) were reduced in dy/dy/mice, and the data indicate a reduction of enzyme activity rather than in efficiency. In dy21/dy21/mice, HCG-induced T synthesis was increased, HCG-induced E2 synthesis was normal, but basal media E2 levels were reduced, with the in vitro efficiency of aromatase being suppressed under both basal and HCG-stimulated conditions, when compared to their normal littermates.

17-Hydroxysteroid Dehydrogenases↗
PubMed1991

Guiding catheter-assisted renal artery angioplasty.

A guiding catheter was used in seven patients who underwent balloon dilation of nine renal arteries. The advantages of using a guiding catheter for renal angioplasty are analogous to the benefits obtained with a coronary angioplasty guiding catheter used in coronary angioplasty. The guiding catheter provides back-up support to cross lesions and allows selective contrast visualization of the lesion before, during, and after dilation. It is also possible, when using a guiding catheter, to measure pressure gradients across lesions without having to recross the lesion which may help to ensure that adequate dilation of the stenosis has been accomplished.

Aged↗
PubMed1991

Recanalization of arterial occlusions with a lensed fiber and a holmium:YAG laser.

Laser recanalization of totally occluded swine iliac arteries was performed to assess the safety and efficacy of a lensed fiber laser angioplasty system with a holmium:YAG (2.1 microns) laser. Silica lenses of 1.0 mm, 1.3 mm, and 1.5 mm in diameter attached to the distal end of a 300-microns diameter silica fiber delivered fluences of 79.5 J/cm2, 31.4 J/cm2, and 25.5 J/cm2, respectively. The pulse duration of the laser was 250 microseconds and the repetition rate was 4 Hz. The mean length of the total occlusions was 5.3 +/- 2.0 cm (range 0.5 cm to 8.0 cm). Successful recanalization was obtained in 16/16 lesions without angiographic vessel perforation. Angiographically significant residual stenoses (greater than 50%) remained in every case following successful laser recanalization. Histologically there was minimal evidence of thermal or acoustic tissue injury; however, in 4 of 16 arteries there was evidence of deep arterial dissection following laser recanalization. We conclude that this lensed fiber coupled with a holmium:YAG laser is a safe and effective method for crossing total occlusions in the relatively straight iliac arteries of this animal model.

Angioplasty, Laser↗
PubMed1991

Exposure to estradiol impairs luteinizing hormone function during aging.

The loss of ovulatory cyclicity in many mammals is caused by changes in the hypothalamic-pituitary (H-P) control of the preovulatory luteinizing hormone (LH) surge. This work evaluated the anterior pituitary (AP) component of the H-P axis by determining the ability of perifused AP to release LH following sustained but pulsatile LHRH stimulation. The normal dual discharge profile of LH was affected by age. The first hour of the response, unaffected by cycloheximide, was similar in 5-6-month-old (mature), 12-13-month-old (declining litters) and 16-18-month-old (irregularly cycling) mice. The remaining protein synthesis-dependent part of the response was reduced in the 16-18 and 22-24-month-old (anestrus) mice. The role of estradiol (E2) in AP aging was further tested as AP from ovariectomized (OVXed) mice, deprived of E2 since puberty, responded as well as the mature proestrous group. In contrast, aged mice subjected to long-term E2 exposure (cycling or OVXed plus E2 replacement) failed to produce the dual response pattern. Since alterations in LH response occurred during the protein-dependent phase, synthetic processes that involve packaging and transport of stored LH, or the production of new LH, may be affected by age. Furthermore, E2 is a major factor in altering LH function and appears to act before middle age.

Aging↗
PubMed1991

Percutaneous angioscopy during coronary angioplasty using a steerable microangioscope.

The feasibility of using a flexible, steerable angioscope to perform coronary angioscopy before and after percutaneous coronary angioplasty was tested. The microangioscope fits through an 8F coronary angioplasty guiding catheter and contains a multifiber viewing bundle incorporated into the body of a 4.3F balloon catheter with a central lumen for distal flushing and guide-wire passage. Angioscopy was performed without complications 45 times in 24 patients, including 6 patients with stable and 18 with unstable angina. Circumferential visualization of the target lesion was successful in 20 (83%) of the 24 patients and improved with operator experience. Excellent visualization of the target lesion was achieved in 16 (94%) of the last 17 patients. Plaque, thrombus and dissection were among the abnormal findings in the 20 patients (4 with stable, 16 with unstable angina) in whom circumferential viewing of the target lesion was achieved. In four patients with restenosis after angioplasty, the lesion morphology was distinctly different from that of lesions in arteries without prior angioplasty. In patients with stable angina, no thrombus or dissection was seen by angiography or angioscopy before angioplasty. In patients with unstable angina, thrombus was detected more frequently by angioscopy than by angiography before angioplasty (8 versus 2 of 16) and after (15 versus 2 of 16) angioplasty. Intimal dissection was also seen much more frequently by angioscopy than by angiography before angioplasty (7 versus 0 of 16) and after angioplasty (16 versus 7 of 16). It is concluded that high resolution percutaneous coronary angioscopy can be performed safely in conjunction with balloon angioplasty. Further investigation is needed before this diagnostic tool can be applied clinically.

Angina Pectoris↗
PubMed1991

Percutaneous coronary angioscopy in patients with restenosis after coronary angioplasty.

Percutaneous transluminal coronary angioscopy with a flexible steerable microangioscope was performed in five patients undergoing repeat angioplasty. Recurrent lesions were assessed by angioscopy before and after the angioplasty procedure. The most common surface morphology observed in these restenosis lesions was that of white unpigmented lesions consistent with the proliferation of fibrous tissue. Also noted during angioscopy was the presence or absence of thrombus or dissection in association with the lesions either before or after angioplasty. Filmy wisps of tissue, presumably intimal flaps, were commonly visualized after angioplasty. There were no complications related to angioscopy or angioplasty in these patients. The surface morphology of restenosis lesions appears to be different from that of primary atherosclerotic lesions. The lesions in these five patients with restenosis were generally white and fibrotic in appearance, as opposed to the pigmented yellow to yellow-brown lesions commonly seen in undilated atherosclerotic lesions. It was also noted that the presence of intracoronary thrombus was strongly associated with the clinical syndrome of unstable angina. These findings support the hypothesis that restenosis lesions are the result of a reparative process consisting of smooth muscle cell proliferation and fibrosis.

Adult↗
PubMed1991

Levels of alpha-inhibin in aging female mice.

alpha-inhibin was immunocytochemically localized in granulosa cells of different stages of developing follicles, freshly formed corpora lutea, and scattered interstitial cells (pigmented or ceroid cells) in ovaries of 6-, 14-, and 23-25-mo-old C57BL/6NNia mice. Developing follicles exhibited the greatest amount of staining. Quantitation of the stain using an image analysis system indicated the staining intensity within ovarian follicles of 14-mo-old mice was greater than that in 23-25-mo-old mice. The levels of plasma alpha-inhibin and estradiol (E2) decreased with age. The number of follicles present in ovaries of middle-aged mice was comparable to those of 6-mo-old mice, yet plasma levels of FSH were significantly higher than those of 6-mo-old mice. This may be due to an age-related loss in the sensitivity of the hypothalamus and/or pituitary of middle-aged mice to ovarian hormones. In contrast, ovaries of 23-25-mo-old mice contained few antral follicles and consequently produced little alpha-inhibin. There appeared to be little negative feedback regulation of FSH secretion in 23-25-mo-old mice as a result of age-related ovarian impairments. This study supports an earlier hypothesis from our laboratory [Biol Reprod 1985; 32:989-997] that the primary defect(s) limiting age-related reproductive performance in mice appears to reside within the hypothalamo-hypophyseal axis, whereas secondary defects arise from the ovary.

Aging↗
PubMed1990

The use of mouse pituitary fragments to study LH secretion.

This work evaluated a perifusion system for studying LH secretion from the anterior pituitary (AP) of female mice. Pituitary fragments were challenged with LHRH, and the effluents assayed for LH. In general, the tissue exhibited augmented release to repeated stimulation. In the dose-response study, the amount of LHRH required to produce maximum and half maximum responses dropped almost 10 fold by the 3rd stimulus. In response to various pulse frequencies LH release increased with the frequency of the 100 nM LHRH dose, but the tissue became refractive to constant nonpulsatile stimulation. Other preparations, subjected to high-frequency 10 nM LHRH pulses, released LH in two distinct episodes. All but the first hour of the response was blocked by cycloheximide, confirming the role of protein synthesis in the sustained release of LH. By varying both the pulse frequency and amplitude, a LHRH protocol was found that produced a proestrous-like surge. Lastly, rat and mouse tissues responded similarly to pulsatile LHRH, verifying their similar LH function during the preovulatory period. These studies demonstrate that the perifusion technique can be used for studying LH secretion in the mouse. Its application to other mouse-oriented studies is planned.

Animals↗