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Biomedical subjects

C Proctor

Publications and source records attributed to C Proctor.

At least 19 recordsLinked to original sources
PubMed1998

Effects of doxycycline on human prostate cancer cells in vitro.

Prostate cancer is the most common form of cancer in older men and the major cause of death from prostate cancer is metastatic disease. The matrix metalloproteinases (MMPs) play a significant role in the growth, invasion and metastasis of many tumors, including those of the prostate. We previously demonstrated that doxycycline, a synthetic tetracycline, inhibits MMPs and cell proliferation and induces apoptosis in several cancer cell lines. We also demonstrated that in an in vivo model of metastatic breast cancer in athymic mice doxycycline inhibits tumor size and regrowth after resection. In the present study, gelatinolytic activity in the human prostate cancer cell line, LNCaP, was suppressed and significant inhibition of cell growth occurred after exposure to 5 or 10 microg/ml of doxycycline, while cell growth was normal in untreated cells. Radioisotope incorporation into proteins was reduced by doxycycline. DNA fragmentation, consistent with apoptosis, was demonstrated in cells treated with doxycycline. These data suggest that doxycycline may have potential utility in the management of prostate cancer.

Adenocarcinoma↗
PubMed1997

Effects of vitamin D3 on proliferation of cancer cells in vitro.

The principal cause of death from most forms of cancer is metastatic disease. Cancer cells appear to grow quickly out of the control of the normal host regulatory mechanisms. Many factors contribute to this unrestrained proliferation, including increased metalloproteinase activity causing degradation of the extracellular matrix surrounding cancer cells, angiogenesis permitting easy access of the cells to the bloodstream and decrease or loss of programmed cell death, or apoptosis, an important mechanism for removal of abnormal or senescent cells. Treatment modalities targeted towards arresting cancer cell proliferation and spread are needed to improve the survival of patients with cancer. Vitamin D3, 1,25-dihydroxychole-calciferol D3, has been shown to induce apoptosis in the human breast cancer cell line, MCF-7. We have studied the effects of three concentrations of vitamin D3 on the human breast cancer cell line, MDA-MB-435, the human prostate cancer cell line, LNCaP, and a human osteosarcoma cell line, U20S. We report here that vitamin D3 strikingly inhibits cell proliferation and induces apoptosis in all three cell lines.

Adenocarcinoma↗
PubMed1997

Inhibition of proliferation and induction of apoptosis by doxycycline in cultured human osteosarcoma cells.

Matrix metalloproteinases (MMPs) play a major role in the phenomena of growth, invasion, and metastasis of malignant disease. We studied the effects of doxycycline, a synthetic tetracycline that has been shown to suppress MMP activity in other solid tumors, on osteosarcoma (OSA) cell proliferation and MMP activity in vitro. OSA cells from 6 patients and from one established human tumor cell line (U2OS) (American Type Culture Collection) were cultured in the presence or absence of doxycycline. Doxycycline (10 microg/ml) suppressed OSA cell proliferation threefold to sevenfold in all cultures. MMP activity was assessed by gelatin zymography and was diminished by approximately 50% in all cultures. We examined the hypothesis that induction of apoptosis is one of the mechanisms by which doxycycline inhibits OSA cell proliferation. Ethidium bromide-stained gels of DNA from cells grown in the presence of 5 microg/ml and 10 microg/ml of doxycycline revealed laddering consistent with apoptosis after 24 hours in culture. The demonstration that doxycycline suppresses cell proliferation and MMP activity and induces apoptosis in human OSA cells in vitro suggests that this well-tolerated oral agent may be effective in the in vivo treatment of OSA.

Apoptosis↗
PubMed1996

Assessment of donor cell and matrix survival in fresh articular cartilage allografts in a goat model.

The long-term survival of allografts of articular cartilage has been proposed to be dependent on the survival of the cells that maintain the unique structural and material properties of the allograft. In this study, we assessed cell survival in 24 fresh articular cartilage allografts of the medial plateau in a Spanish-goat model. A DNA-probe technique was used to distinguish clearly between DNA from donor (allograft) and host cells. The intraarticular survival of viable allograft chondrocytes in the transplanted articular cartilage started to diminish as early as 3 weeks after transplantation; however, there was considerable variation in the amount of donor cell DNA detected in the allografts at 6 and 12 months following transplantation. This contrasts with our experience with fresh allografts of ligament, tendon, and meniscus, in which no donor DNA was detected 4 weeks after transplantation. DNA from host cells was present in all articular cartilage allografts, as evidenced by detectable unique host DNA patterns. Histological and histochemical assays showed that none of the transplants demonstrated normal structure and composition at 1 year after transplantation. The grafts in which large quantities of donor DNA were present appeared grossly superior to those with no or reduced remaining demonstrable donor DNA.

Animals↗
PubMed1994

Studies of copper transport in cultured bovine chondrocytes.

Copper serves as the cofactor for a number of important enzymes in cartilage, as well as in other tissues, including lysyl oxidase, superoxide dismutase, and cytochrome oxidase. Ceruloplasmin is responsible for the transport of approx. 95% of the copper in serum, but the mechanisms for intracellular copper transport are unknown. We have demonstrated recently that a high-molecular-weight cartilage glycoprotein, referred to as CMGP, has regions of sequence homology with ceruloplasmin. CMGP also binds copper and has at least some oxidase activity similar to that of ceruloplasmin. Other tissues synthesize intracellular ceruloplasmin-like proteins. The present report represents part of an effort to examine the hypothesis that CMGP is a copper transport protein in chondrocytes and to characterize the enzymatic activities of CMGP. These studies demonstrate that CMGP is the principal chondrocyte protein labeled by 67Cu in vitro and that the label is localized to the mitochondria, cytosol, and membrane fractions of sucrose gradients, suggesting copper transport through the cell. In parallel experiments, [3H]leucine was incorporated into proteins corresponding to the subunits and fragments of CMGP, as described previously, and in a similar distribution among the subcellular fractions as labeled copper. Additionally, CMGP has oxidase and ferroxidase activities similar to those of ceruloplasmin.

Animals↗
PubMed1993

Evidence that a 550,000-dalton cartilage matrix glycoprotein is a chondrocyte membrane-associated protein closely related to ceruloplasmin.

Cartilage matrix glycoprotein (CMGP) is a disulfide-bonded 550,000-dalton protein that is synthesized by chondrocytes and ciliary epithelial cells. We have purified the protein from bovine and porcine articular cartilage and have sequenced two peptides, which both have significant homology with human ceruloplasmin, a copper-binding oxidase. Immunolocation analysis indicates that a commercial polyclonal antiserum to human ceruloplasmin reacts with bovine cartilage CMGP. Chelating columns made with copper bind CMGP from bovine cartilage extracts. CMGP is present in bovine chondrocyte membrane preparations purified from sucrose density gradients. Oligonucleotide probes have been synthesized based on the published sequence of the 3'-untranslated region and a portion of the C terminus of human ceruloplasmin and have been used to amplify a cDNA fragment from bovine cartilage and human liver libraries. CMGP demonstrates oxidase activity towards p-phenylenediamine similar to that of ceruloplasmin. These studies suggest that CMGP is closely related to, if not identical with, ceruloplasmin. It is possible that CMGP may be involved in metal transport into and/or within the chondrocyte.

Amino Acid Sequence↗
PubMed1989

Transurethral prostatectomy: practice aspects of the dominant operation in American urology.

In a national survey of all American urologists transurethral prostatectomy accounted for 38 per cent of the major surgical procedures performed by the respondents. They regarded the operation as complex and they believe achievement of proficiency requires that more be performed during residency training than any other urological operation. Furthermore, they assigned transurethral prostatectomy a significantly higher relative value than have medical economists doing research in the field of physician reimbursement. The effect of recent legislated congressional reductions in the allowable Medicare fees for transurethral prostatectomy is discussed along with the impact of these reductions on urological patient care and the American urologist. Practice patterns and geographic variations in the costs of transurethral prostatectomy also are considered.

Adult↗
PubMed1987

Cocaine-sensitive O-methylation of noradrenaline in dental pulp of the rabbit: comparison with the rabbit ear artery.

Incisor pulp from the rabbit metabolises exogenous noradrenaline in concentrations between 0.12 and 1.2 mumol/l mainly to NMN. Effects of chronic sympathetic denervation indicated that in incisor pulp the NMN is extraneuronal in origin, and that DOPEG and DOMA formation, as well as a major part of the noradrenaline which accumulates in the tissue, are associated with the sympathetic nerves. NMN formation was unaffected by hydrocortisone 210 mumol/l, but was strongly inhibited by cocaine 30 mumol/l. These effects contrasted with those in the rabbit ear artery, where NMN formation was increased by cocaine 30 mumol/l and decreased by hydrocortisone 210 mumol/l. In COMT-inhibited denervated pulp, cocaine inhibited the accumulation of noradrenaline. Monoamine fluorescence histochemistry of pulp exposed to noradrenaline 50 mumol/l indicated that cocaine-sensitive uptake occurred in fibroblasts. It is concluded that O-methylation of noradrenaline in dental pulp involves prior uptake of the amine by a process resembling uptake1 but which is distinguished from uptake1 by its extraneuronal location.

Animals↗
PubMed1987

A study of the atmosphere in London underground trains before and after the ban on smoking.

Measurements of the ambient atmosphere in London Underground train compartments were made before and after a ban on smoking. Levels of nicotine and carbon monoxide and estimates of airborne particulates are given. This paper describes the analytical techniques used in measuring constituents of tobacco smoke in the ambient air of public environments. Levels observed were all found to be far lower than recommended OSHA limits for safe exposure.

Aerosols↗
PubMed1986

A new use for M-mode echocardiography in detecting left ventricular diastolic dysfunction in coronary artery disease.

Regional left ventricular (LV) diastolic function affects the global rate and pattern of LV filling. These changes may be detected by changes in the magnitude and timing of the increase in LV basal diameter during diastole. Because M-mode echocardiography possesses the high temporal and spatial resolution to detect such abnormalities, a group of 8 normal control subjects were compared with a group of 12 patients with coronary artery disease (CAD) to determine differences in the rate and timing of ventricular filling. The CAD patients had lower rates of fast filling expansion than the control subjects. The proportion of LV diastolic expansion during fast filling was lower. During atrial systole the increased rate of LV expansion was not significantly higher in the CAD patients, but the proportion of diastolic expansion occurring with atrial systole was increased. These changes may reflect a decrease in the rate and magnitude of early diastolic filling in the noncompliant ventricle and an increased reliance on active atrial transport. Thus, CAD alters the rate and pattern of LV filling. Changes in LV diameter as measured by M-mode echocardiography may be useful in detecting altered patterns of LV diastolic filling and identifying patients with CAD.

Adult↗
PubMed1986

Role of sympathetic nerves in the metabolism of exogenous noradrenaline in rabbit gingival tissue and ear artery.

Uptake and metabolism of 3H-noradrenaline 0.18 mumol/l was examined in rabbit gingival slices and ear artery segments. The tissues were incubated with the 3H-amine for 30 min. The artery accumulated approximately ten times more of the 3H-amine and generated four times more 3H-metabolites than the gingiva. In both tissues, chronic sympathetic denervation resulted in marked decreases in 3H-noradrenaline accumulation and deamination. An inhibitor of sympathetic neuronal uptake, cocaine 30 mumol/l, strongly inhibited the firmly-bound component of 3H-noradrenaline accumulation by the tissues and strongly decreased the accumulation of deaminated metabolites in the incubating medium. It is concluded that the sympathetic nerve terminals play an important role in the accumulation and deamination of noradrenaline in the gingiva and in the artery. Chronic sympathetic denervation resulted in increased 3H-normetanephrine (NMN) formation by the gingiva and the artery, indicating that in both tissues the noradrenaline was O-methylated at sites extraneuronal to the sympathetic nerves. Differences between the effects of cocaine in the gingiva and artery, with respect to 3H-NMN accumulation in the incubating medium, are interpreted as evidence that in the gingiva, but not in the artery, cocaine inhibits extraneuronal O-methylation, as well as neuronal uptake, of noradrenaline.

Animals↗
PubMed1985

Purulent meningococcal pericarditis: chronic percutaneous drainage with a modified catheter aided by echocardiography.

A 7-month-old infant presented with suspected sepsis. On the third day of illness signs of cardiac tamponade developed. Tamponade was relieved by pericardiocentesis, and countercurrent immunoelectrophoresis (CIE) analysis of the fluid was positive for meningococcus group B. Antibiotic treatment was changed to penicillin G. After echocardiography demonstrated reaccumulation of fluid, a modified #16 gauge angiocatheter was placed percutaneously in the pericardial space. When drainage slowed it was repositioned using two-dimensional echocardiography. After 24 h the catheter was removed and no further accumulation occurred. The antibiotics were continued an additional 10 days and the infant recovered uneventfully. Modification of the catheter and echographic repositioning may decrease the need for surgical drainage in such patients.

Cardiac Catheterization↗
PubMed1982

Prior hot plate exposure enhances morphine analgesia in tolerant and drug-naive rats.

The associative model of morphine tolerance predicts that established tolerance should be attenuated, i.e., extinguished, by placebo injections in the former morphine injection environment. The present study examined the effect of placebo sessions, with and without accompanying nociceptive stimulation, on the extinction of analgesic tolerance. In Experiment 1, rats rendered tolerant to morphine displayed recovery of morphine's analgesic action only following placebo sessions including exposure to a painful hot plate surface (52.5 degrees C); placebo sessions on a cool plate (23-24 degrees C) failed to attenuate tolerance even though these placebo sessions more closely matched the stimulus conditions of tolerance acquisition. In Experiment 2, repeated hot plate exposures were similarly found to enhance morphine analgesia in drug-naive rats. These results question an extinction account of the effect of hot plate placebo sessions observed in Experiment 1. Instead, they suggest that nociceptive hot plate exposures, per se, are sufficient to enhance subsequent morphine analgesia.

Animals↗
PubMed1972

Tympanoplasty.

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Cholesteatoma↗