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Biomedical subjects

S G Brown

Publications and source records attributed to S G Brown.

At least 19 recordsLinked to original sources
PubMed1991

Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples.

Human plasma contains an inhibitor of tissue factor-initiated coagulation known as the lipoprotein-associated coagulation inhibitor (LACI) or also known as the extrinsic pathway inhibitor (EPI). A competitive fluorescent immunoassay was developed to measure the plasma concentration of LACI in samples from normal individuals and patients with a variety of diseases. The LACI concentration in an adult control population varied from 60% to 160% of the mean with a mean value corresponding to 89 ng/mL or 2.25 nmol/L. Plasma LACI levels were not decreased in patients with severe chronic hepatic failure, warfarin therapy, primary pulmonary hypertension, thrombosis, or the lupus anticoagulant. Plasma LACI antigen was decreased in some, but not all patients with gram-negative bacteremia and evidence for disseminated intravascular coagulation. Plasma LACI levels were elevated in women undergoing the early stages of labor (29%), in patients receiving intravenous tissue-type plasminogen activator (45%), and in patients receiving intravenous heparin (375%). A radioligand blot of the pre- and post-heparin plasma samples shows the increase to be in a 40-Kd form of LACI. Very low levels of plasma LACI antigen were found in patients with homozygous abetalipoproteinemia and hypobetalipoproteinemia, diseases associated with low plasma levels of apolipoprotein B containing lipoproteins. Following the injection of heparin into one patient with homozygous abetalipoproteinemia, the plasma LACI antigen level increased to a level comparable with that in normal individuals after heparin treatment.

Abetalipoproteinemia↗
PubMed1989

Functional significance of the Kunitz-type inhibitory domains of lipoprotein-associated coagulation inhibitor.

Blood coagulation can be initiated when factor VII or VIIa, a plasma protease, binds to its essential cofactor, tissue factor (TF), and proteolytically activates factors IX and X, triggering a cascade of events which eventually leads to the formation of thrombin and a fibrin clot. Plasma contains a lipoprotein-associated coagulation inhibitor (LACI) which inhibits activated factor X (Xa) directly and, in a Xa-dependent way, inhibits VII(a)/TF activity, presumably by forming a quaternary Xa/LACI/VII(a)/TF complex. Sequence analysis of complementary DNA clones has shown that LACI contains three tandemly repeated Kunitz-type serine protease inhibitory domains. To investigate the relationship between these Kunitz structures and LACI function, we have used site-directed mutagenesis to produce altered forms of LACI in which the residue at the active-site cleft of each Kunitz domain has been individually changed. The second Kunitz domain is required for efficient binding and inhibition of Xa, and both Kunitz domains 1 and 2 are required for the inhibition of VIIa/TF activity; but alteration of the active-site residue of the third Kunitz domain has no significant effect on either function. We propose that in the putative inhibitory complex, Kunitz domain 1 is bound to the active site of VII(a)/TF and that Kunitz domain 2 is bound to Xa's active site.

Humans↗
PubMed1989

Should intramuscular vitamin K prophylaxis for haemorrhagic disease of the newborn be continued? A decision analysis.

Haemorrhagic disease of the newborn is now a rare life threatening disease due to the widespread use of effective prophylaxis with vitamin K at birth. In recent years the continued need for routine prophylaxis has been questioned and alternative strategies proposed. We have reviewed the literature and using techniques of decision analysis, we reaffirm the need for continued prophylaxis. The cost for each life saved by an oral programme is $4500 and $11,000 for intramuscular prophylaxis. The cost to the state of no prophylactic programme is $6.40 per child born and $0.81 for an oral prophylactic programme. It is recommended that the oral route of vitamin K prophylaxis be adopted as it is equally efficacious with the intramuscular route, but cheaper, more consumer acceptable, and has a lower risk of iatrogenic disease.

Administration, Oral↗
PubMed1989

Laser angioplasty with a pulsed NdYAG laser: early clinical experience.

Since December 1986, 40 laser angioplasty procedures have been performed using the energy from a pulsed NdYAG laser, delivering near infrared light (1064 nm) in 100-microseconds pulses of approximately 300 mJ per pulse, directly through a transparent sapphire tipped device. All patients had total occlusion of the superficial femoral artery and symptoms severe enough to warrant surgery, with ulceration or gangrene in eight, rest pain in 14 and severe claudication interfering with life-style in the others. The device was introduced through an antegrade puncture of the superficial or common femoral artery and laser recanalization was followed by attempted balloon angioplasty in all cases. Occlusions were a median length of 15 cm (range 2-35 cm); ten patients had previously undergone failed attempts at conventional balloon angioplasty and four had occluded femoropopliteal grafts. Thirty-seven legs of 34 patients were treated with an average of 60 J (range 10-235 J) with successful recanalization in 27 and immediate reocclusion in seven. The 20 successful recanalizations have been followed up for up to 24 months (median 7 months) with only one late occlusion at 5 months. Failed recanalization was due to poor transmission by the delivery device in the early part of the series (five cases), repeated passage of the device down a collateral branch (four cases), dissection at the site of previous surgery (two cases) or no apparent reason (two cases). Immediate reocclusion was due to very poor run off in patients with severely ischaemic limbs (three cases) or technical difficulties with balloon dilatation (two cases). Complete symptomatic relief was obtained in all the cases of radiologically successful laser angioplasty. Early surgery was required in one case following reocclusion of the artery when an angioplasty balloon failed to deflate, and one patient suffered a skin reaction thought to be due to inadequate removal of the sterilizing solution. A different sterilizing procedure is now followed. Laser angioplasty can reduce the number of patients requiring bypass surgery and improvements in the device and access methods may reduce the number of untreatable cases.

Adult↗
PubMed1989

Concentration of vitamin B6 and activities of enzymes of B6 metabolism in the blood of alcoholic and nonalcoholic men.

The purpose of this study was to compare concentrations of vitamin B6 compounds and the activities of enzymes that synthesize or catabolize pyridoxal 5'-phosphate in the plasma and erythrocytes of nonalcoholic and alcoholic subjects. Blood was obtained from male nonalcoholics and chronic alcoholics with minimal liver damage and normal hematology. Plasma, erythrocyte, and urinary B6 compounds were analyzed by high performance liquid chromatography, and pyridoxal phosphate was also measured enzymatically. Erythrocyte pyridoxine kinase and pyridoxine phosphate oxidase and erythrocyte and plasma pyridoxine phosphate phosphatases were assayed. Plasma pyridoxal phosphate concentration was significantly lower in the alcoholics (31.3 +/- 3.6 nmol/liter) than in the nonalcoholics (58.7 +/- 7.5 nmol/liter). The concentrations of the other B6 compounds in plasma, erythrocytes, and urine were not different in the two groups. Plasma alkaline pyridoxine phosphate phosphatase activity was significantly higher in the alcoholics (4.05 +/- 0.36 nmol/(h.mg] than in the nonalcoholics (3.01 +/- 0.18 nmol/(h.mg]. The activities of erythrocyte kinase, oxidase, and phosphatases were not significantly different in the two groups. The relationship of plasma pyridoxal phosphate concentration to its metabolites and the activities of the enzymes involved in its metabolism was determined. Plasma pyridoxine phosphate phosphatase activity assayed at pH 9.0 or 7.4 correlated negatively with plasma pyridoxal phosphate concentration. The low pyridoxal phosphate concentration observed in the plasma of the alcoholic subjects may in part be related to increased plasma phosphatase activity.

Adult↗
PubMed1989

Improved comfort and patient acceptance in a novel transdermal nitroglycerin delivery system.

Sixty-three angina patients were recruited to participate in a two-week, randomized, open-label, crossover, multicenter trial to compare patient acceptance of two transdermal nitroglycerin delivery systems, Minitran and Transderm-Nitro (TDN). Patients were enrolled if they had stable angina and had been on a stabilized dose (5, 10, or 15 mg/24 hr) of Nitro-Dur II (ND II) for at least one month before entering the study. Patients with a bias against TDN or with any of the contraindications for transdermal nitroglycerin therapy were excluded. During the two consecutive one-week treatment periods, the patients received their prestudy dose regimen of Minitran and TDN in random order. Patients completed daily diaries, weekly questionnaires, and poststudy patient preference evaluation forms. Of the 63 patients who completed the study, 70% preferred Minitran overall (P less than or equal to 0.001), 24% preferred TDN, and 6% had no overall preference.

Adhesiveness↗
PubMed1988

Rapid, inexpensive quality control of fluorine-18 2-deoxy-2-fluoro-D-glucose preparations using the hexokinase reaction in vitro.

A rapid enzymatic method for determining the purity of 2FDG preparations has been devised. A small aliquot of the preparation is incubated with a hexokinase/adenosine triphosphate/Mg+2 mixture and passed through a Dowex 1 ion-exchange column, which retains the 2FDG-6-phosphate. Another aliquot, without prior incubation, is passed through an identical column and the 2FDG radioactivity is found in the eluant. The criteria for purity are quantitative retention of the 2FDG-6-phosphate on the column and no retention of 2FDG. Comparison of the HK method with thin layer and high performance liquid chromatography assays indicate that the HK method can serve as a rapid, simple and inexpensive alternative to these other methods. It can be used in a routine quality control program and may be easily adaptable to automated 2FDG synthetic methods.

Chromatography, High Pressure Liquid↗
PubMed1986

Microenvironment around the essential cysteine residues in chicken liver fructose-1,6-bisphosphatase as analyzed by ESR spin labelling.

Chemical modification and electron spin resonance spectroscopy (ESR) spin-labelling techniques have been employed to investigate the local environment of the essential sulfhydryl groups of chicken liver fructose-1,6-bisphosphatase. The results demonstrate the presence of two distinct classes of sulfhydryl groups in this enzyme. The first class react preferentially with iodoacetate and its spin-labelled derivative, and this results in an increase in catalytic activity, while the second class react preferentially with N-ethylmaleimide and its spin-labelled derivative, and this leads to a decrease in catalytic activity. The ESR spectral data strongly suggest that the first class of sulfhydryl groups are located in a deep cleft of the enzyme molecule, while the second class of sulfhydryl groups are located in a shallow crevice. The environment of the second class of the sulfhydryl groups appears to undergo a significant change after the modification of the first class of sulfhydryl groups by iodoacetate.

Animals↗
PubMed1986

Laser endoscopy.

Explore the source record for details and available documents.

Endoscopy↗
PubMed1979

Search for human tumour viruses by transfection: uptake of melanoma and Epstein-Barr virus DNA by human cells.

In a model system, consistent transfection of chick embryo fibroblasts (CEF) by DNA from the XC cell line occurred, with recovery of infectious Rous sarcoma virus. The techniques were then applied in attempts to recover possible human tumour viruses. Even with various modifications of the XC technique, DNA from three human malignant melanoma cell lines failed to infect adult or foetal human fibroblasts, although melanoma DNA was taken up into nuclei of target cells. XC DNA did not transfect human foetal fibroblasts and melanoma DNA was ineffective in CEF. DNA from the Raji (Epstein-Barr virus non-producer) and QIMR-WIL (producer) lymphoblastoid cell lines did not transfect human cord blood lymphocytes or amnion cells. These broadly applicable techniques therefore failed to recover EB virus, the putative melanoma retrovirus, or other potential tumour virus.

Animals↗
PubMed1979

Cytotoxicity studies of human melanoma cells and fibroblasts.

In seven human melanoma cell lines and one human fibroblast strain some correlation of resistance to cell killing was found with two bifunctional alkylating agents (melphalan, chlorambucil) and three monofunctional agents (4(5)-(3,3-dimethyl-l-triazeno)imidazole-5(4)-carboxamide (DTIC), methylmethane sulphonate (MMS) and N-methyl-N1-nitro-N-nitrosoguanidine (MNNG), but little cross-resistance was found between these two groups of agents or with cytosine arabinoside (ara-C). In contrast to previous studies with rodent tumours, potentially synergistic (chloroquine, arginine) or antagonistic (ascorbic acid, leucine) compounds did not affect the toxicity of melphalan in a human melanoma cell line. In two melanoma lines DTIC induced patterns of DNA damage (inhibition of semi-conservative synthesis) and repair (strand breaks and repair synthesis) similar to, but not identical with, those induced by the methylating agent MMNG. These results suggest that a methylating species is derived from DTIC but has a different reactivity toward DNA compared with MNNG.

Animals↗
PubMed1975

Plate fixation of iliac shaft fractures in the dog.

In a series of 20 dogs, 23 fractured ilia were reduced and stabilized with a variety of bone plates. The results indicated that fixation was rigid enough for fracture healing and for the patient to be ambulatory soon after surgery. Plate fixation can therefore be recommended as a reliable method of repair in selected fractures of the canine ilium.

Acetabulum↗