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Biomedical subjects

C S Jones

Publications and source records attributed to C S Jones.

At least 91 records · Page 5Linked to original sources
PubMed1990

Biochemical and growth inhibition studies of methotrexate and aminopterin analogues containing a tetrazole ring in place of the gamma-carboxyl group.

The biological activities of novel analogues of methotrexate (MTX) and aminopterin (AMT) in which the gamma-carboxyl was replaced by a 1H-tetrazol-5-yl ring, an isosteric group with acidic properties similar to a carboxyl group, were investigated. The tetrazolyl analogues of MTX and AMT were more potent inhibitors of the growth of CCRF-CEM and K562 human leukemia cell lines during continuous (120 h) and 24-h pulse exposure than were the respective parent drugs; only when the exposure time was reduced to 6 h were the parent drugs more potent. These inhibitory effects on growth correlated with the onset of and recovery from inhibition of de novo thymidylate biosynthesis. Growth inhibition by the analogues was protectable by leucovorin. MTX-resistant CCRF-CEM sublines with decreased transport or increased dihydrofolate reductase (DHFR) levels were cross-resistant to the analogues. The analogues were as potent as their parent drugs in inhibiting DHFR activity in vitro and at displacing [3H]MTX from intracellular DHFR. Each analogue was more effective than its parent drug at inhibiting uptake of [3H]MTX into CCRF-CEM cells. The tetrazole analogue of AMT was a linear competitive inhibitor (Kis = 50 microM) of CCRF-CEM folylpolyglutamate synthetase, while the tetrazole analogue of MTX, unlike all other inhibitors, was linear noncompetitive (Kis = 51 microM, Kii = 321 microM). The data suggest that, compared with MTX or AMT, the tetrazole substituent, in place of the gamma-carboxyl group, allows more efficient transport into cells via the reduced folate/MTX carrier and the resulting greater uptake of the analogues leads to inhibition of DNA synthesis and cell death at lower extracellular concentrations during long exposures. The mechanism of cell death could involve inhibition at folypolyglutamate synthetase, but DHFR is the primary target. The low potency of the analogues during short exposure is presumably related to the inability to form the poly-gamma-glutamyl metabolites required for intracellular retention.

Aminopterin↗
PubMed1990

The role of emergent exploration in free-tissue transfer: a review of 150 consecutive cases.

One-hundred and fifty consecutive free-tissue transfers were reviewed to evaluate the role of emergent exploration in flap survival. Eleven flaps exhibited signs of circulatory failure between 1 hour and 6 days postoperatively and required return to the operating room. In eight patients the preoperative diagnosis was venous thrombosis, and in three patients it was arterial thrombosis. The average time from the first abnormal examination to exploration was 1.5 hours. There were no false-positive explorations. All 11 flaps were salvaged following correction of the cause of circulatory compromise. In eight patients this was due to inflow or outflow obstruction in the recipient vessels proximal to the anastomosis, in two patients it was due to extrinsic compression of the flap from a tight wound closure, and in one patient it was due to obstruction of the recipient vein by a drain. Primary anastomotic thrombosis was not encountered as the cause of circulatory compromise in any patient. An aggressive approach to exploration was responsible for an increase in flap survival in the entire series from 90 to 98 percent. The results of this study demonstrate the efficacy of clinical monitoring, the role of early exploration, and the durability of microvascular anastomoses.

Adolescent↗
PubMed1989

Interaction of free porphyrins and metalloporphyrins with mouse ferrochelatase. A model for the active site of ferrochelatase.

The ability of purified mouse ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) to bind and catalytically utilize a variety of porphyrins has been examined. In all, the kd, Km or Ki values for eleven different porphyrins, the Ki values for four metalloporphyrins and the kd values for two metalloporphyrins were determined. The data obtained demonstrate that mouse ferrochelatase binds a wide variety of porphyrins and metalloporphyrins with kd values ranging from 6 nM for N-methylprotoporphyrin to 1.08 microM for coproporphyrin III. However, the enzyme shows a degree of catalytic specificity for the substituents at the 2.4 positions and utilizes only proto-, hemato-, meso-, deutero-, 2,4-monohydroxy-ethylmonovinyl- and 2,4-monohydroxymethylmonovinyl deuteroporphyrin as substrates. The data show that the magnitude of the kd is not an accurate indicator of the ability of the porphyrin to serve as a substrate or inhibitor and, with the exception of N-methylprotoporphyrin, the size of the kd is several orders of magnitude less than that of the Km or Ki. Of the metalloporphyrins examined (Fe, Co, Zn and Sn) all inhibited ferrochelatase at micromolar concentrations, although tin protoporphyrin was the least effective. These data are discussed in terms of an active site model for mammalian ferrochelatase.

Animals↗
PubMed1989

Fee scales.

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Composite Resins↗
PubMed1989

Self referral to an accident and emergency department for another opinion.

OBJECTIVE: To determine whether patients referring themselves to an accident and emergency department for another opinion after consulting their general practitioner present with serious illness, show any risk factors for being admitted, or are more likely to be patients of particular practitioners. DESIGN: Six month prospective survey. SETTING: District general hospital's accident and emergency department, receiving 42,000 new patients a year. PATIENTS: 180 Patients identified as attending for another opinion having already consulted a general practitioner. INTERVENTIONS: Classified as admission, referral to specialist clinic, follow up in accident and emergency department, or referral back to general practitioner. END POINT: Admission, with an analysis of admitted patients. MEASUREMENTS AND MAIN RESULTS: General outcome, diagnostic category, age, time of attendance, time since seen by general practitioner, and name of general practitioner were recorded. Forty seven patients were admitted, 99 were discharged back to the general practitioner (62 without a letter), and two died. Patients were most likely to be admitted if they attended within 24 hours after seeing a general practitioner, were aged under 5, or presented with respiratory or gastrointestinal complaints. Some general practitioners were overrepresented. CONCLUSIONS: Important disorders present in this way, and therefore these patients should be seen by a doctor. Information about these attendances could be useful to general practitioners in reviewing their performance.

Adolescent↗
PubMed1989

Growth phase dependency of chromatin cleavage and degradation by bleomycin.

Preferential cleavage of Saccharomyces cerevisiae chromosomes in internucleosomal (linker) regions and nonspecific degradation of chromatin by an anticancer antibiotic which degrades DNA were investigated and found to increase in consecutive stages of growth. Cleavage of DNA in internucleosomal regions and intensities and multiplicities of nucleosomal bands were dependent on drug concentration, growth phase of the cells, and length of incubation. Cellular DNA was least degraded during logarithmic phase. After cells progressed only one generation in logarithmic phase, low concentrations (6.7 x 10(-7) to 3.4 x 10(-6) M) of bleomycin produced approximately three to seven times more DNA breaks. Internucleosomal cleavage was highest, and the most extended oligonucleosomal series and extensive chromatin degradation were observed during stationary phase. It is concluded that the growth phase of cells is critical in determining amounts of the highly preferential cleavage in internucleosomal regions and overall breakage and degradation of DNA. Mononucleosomal bands were most intense, indicating the greatest accumulation of DNA of this size. Mean mononucleosomal lengths were 165.9 +/- 3.9 base pairs, in agreement with yeast mononucleosomal lengths. As high-molecular-weight chromatin was digested by bleomycin, oligonucleosomes and, eventually, mononucleosomes became digested. Therefore, it is also concluded that bleomycin degradation of oligonucleosomes and trimming of DNA linker regions proceed to degradation of the monosomes (core plus linker DNA).

Bleomycin↗
PubMed1988

Peptidyl O-acyl hydroxamates: potent new inactivators of cathepsin B.

Peptidyl O-acyl hydroxamates having appropriate active-site recognition features are very potent time-dependent inhibitors of the cysteine proteinase cathepsin B. The inhibition is irreversible, and the inactivation rate is strongly dependent on peptide structure and correct positioning of the P1 amino acid carbonyl group. Lipophilic O-acyl groups provide the most rapid inactivators, as exemplified by the inhibitor O-mesitoyl N-benzyloxycarbonyl-L-phenylalanyl-L-alanine hydroxamate (kmax/Ki = 640,000 M-1s-1).

Animals↗
PubMed1988

Mammary blood flow and cardiac output during initiated involution of the mammary gland in the rabbit.

1. Cardiac output and its distribution to the mammary gland, kidneys, heart, liver and gastrointestinal tract were measured in conscious rabbits at day 1, day 3 and day 6 after removal of the young at day 0. 2. There was no change in cardiac output, proportion of cardiac output delivered to the mammary gland or mammary blood flow 24 hr after the last suckling period. After a further 48 hr there was a significant reduction in the cardiac output, proportion of the cardiac output and blood flow to the mammary gland compared to the values measured in lactating animals. 3. There was no significant difference in blood flow to the other organs although there were changes in the proportion of the cardiac output delivered to the heart, kidney and liver during this period. 4. The change in uptake of glucose, acetate, non-esterified fatty acids and triacylglycerols by the mammary gland are discussed in relation to the reabsorption of milk components.

Animals↗
PubMed1988

Development of neuroendocrine (Merkel cell) carcinoma mixed with squamous cell carcinoma in erythema ab igne.

Squamous cell carcinoma and neuroendocrine (Merkel cell) carcinoma are cutaneous neoplasms that have only occasionally been reported to coexist. Squamous cell carcinoma, but not neuroendocrine (Merkel cell) carcinoma, is a rare complication of erythema ab igne. This report describes the development of both neoplasms arising within the same tumor mass in an area of erythema ab igne.

Aged↗
PubMed1987

On onanism.

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Bible↗
PubMed1987

Glucose kinetics in the oestrogen-treated male chicken (Gallus domesticus), measured after administration of [6-3H]glucose and [U-14C]glucose in vivo.

Male chickens (Gallus domesticus) were treated with 17 beta-oestradiol then injected with a mixture of [6-3H]glucose and [U-14C]glucose. Subsequently, blood samples were taken to determine plasma lipid levels and several parameters of glucose metabolism, including entry rate, carbon recycling, mean transit time, the total body glucose mass, the mass of the sampling pool and the rate of outflow from this pool. Oestrogen-treated birds exhibited typical hyperlipidaemia, with significantly elevated plasma levels of triacylglyerol and nonesterified fatty acids. Oestrogen administration significantly decreased the glucose entry rate, the total body glucose mass and the rate of outflow from the sampling pool.

Animals↗
PubMed1986

Chronic contained rupture of abdominal aortic aneurysms.

Anecdotal reports of chronic contained rupture of abdominal aortic aneurysms exist. Their existence and implications have been largely ignored. From March 1984 to March 1985, 24 patients required repair of an infrarenal abdominal aortic aneurysm. Four patients underwent emergent repair. The remaining 20 patients were evaluated with computed tomography electively. Seven patients (35%) were demonstrated to have a rupture of the aneurysm and a retroperitoneal hematoma on the computed tomographic scan. All of the patients had histories of back or flank pain; five patients continued to complain of mild pain on admission. In no case was shock, impending shock, or a decrease in the hemoglobin level present on admission. All patients were operated on within 24 hours of evaluation. At operation, rupture was noted with organized hematoma outside the aorta contained in a pseudoaneurysmal wall of retroperitoneal connective tissue. There was no intraperitoneal blood. There was no operative mortality and survival was 100% at six months. The CT scan evaluation had identified a subgroup of patients with aneurysms associated with chronic contained rupture.

Aged↗
PubMed1986

Bioprosthesis in hand surgery.

In 1965, Carpentier coined the term bioprosthesis to distinguish the characteristics of glutaraldehyde-treated porcine heart valves from untreated or synthetic valves. Observation that the valves functioned normally but were not incorporated by the host has stimulated interest in similarly preserved materials for use in hand surgery. This report outlines work that was initiated to learn the effects of glutaraldehyde treatment on tendon and a reticular substitute. In over 56 experiments with a chicken model, experience with glutaraldehyde-treated tendon grafts shows no acute rejection. There is good function clinically by 8 weeks with proximal fibrous ingrowth seen histologically. By 12 weeks, distal ingrowth has occurred. There is no ingrowth into the tendon graft within the fibro-osseous tunnel. Mechanical testing of the implant system shows a peak load at failure of 1.86 +/- 0.43 pounds and at 24 weeks it is 6.53 +/- 2.6 pounds. The failure site at time zero was distal. By 12 weeks, the distal attachment strengthened and the proximal attachment failed at a greater load. An interpositional substance with potential uses in hand surgery has been prepared by glutaraldehyde treatment of mammalian pericardium. Possible uses include interposition between fractured phalanx and the extensor tendon. This has been evaluated in feasibility studies in a rabbit model.

Animals↗
PubMed1986

Evaluation of glutaraldehyde-treated tendon xenograft.

Glutaraldehyde-treated flexor tendon xenografts were implanted in 62 adult White Leghorn chickens. Animals were evaluated for implant integrity, function, mechanical tests, and histology serially to 24 weeks. Implant function improved dramatically throughout the 24 weeks. Gross examination at death showed intact proximal and distal attachments in all but two animals. The amount of fibrous ingrowth into the proximal end of the implant increased throughout the 24 weeks. Distal fibrous ingrowth also occurred, but at a slower rate. At no point was lateral ingrowth into the tendon seen within the fibro-osseous tunnel. Excision of the sheath and pulley system significantly limited tendon gliding by allowing vigorous formation of adhesions. Mechanical testing revealed that the distal attachment strengthened with time and that the proximal attachment became the failure point. Glutaraldehyde-treated mammalian tendon xenografts allow for fibrous ingrowth and may become incorporated by the host. In this animal model, it has allowed the xenograft to function as a tendon graft. Further studies are planned before clinical trials are undertaken.

Animals↗
PubMed1986

Characterization of NPS-1, a novel plasmid-mediated beta-lactamase, from two Pseudomonas aeruginosa isolates.

A novel beta-lactamase, which had a pI of 6.5 and a molecular weight of 25,000, was observed in two Pseudomonas aeruginosa isolates. The enzyme, designated NPS-1, was encoded by a plasmid of molecular weight 41 X 10(6) which also encoded resistance to streptomycin and sulfonamide. This plasmid, designated pMLH50, was freely transmissible to other P. aeruginosa strains, but not to Escherichia coli K-12. The enzyme was purified partially and shown to have activity against both penicillins and cephalosporins. Vmax rates for oxacillin and carbenicillin were less than 50% of the Vmax for benzylpenicillin, and the Vmax for cephaloridine was only 3% of the Vmax for benzylpenicillin. Imipenem, aztreonam, and several antipseudomonal cephalosporins were stable to the enzyme. Hydrolysis of most substrates obeyed Michaelis-Menten kinetics, but cefsulodin induced a reversible reduction in the activity of the enzyme. Transconjugants of the beta-lactamase-producing isolates in P. aeruginosa PU21 acquired beta-lactam resistances which mirrored the hydrolytic activity of the enzyme.

Anti-Bacterial Agents↗