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Biomedical subjects

P Blackburn

Publications and source records attributed to P Blackburn.

At least 19 recordsLinked to original sources
PubMed1997

Do intact viral particles survive excimer laser ablation?

OBJECTIVE: To determine if intact and potentially infectious viral particles can withstand excimer laser ablation and possibly pose a health hazard to medical personnel. METHODS: Excimer laser ablation of fibroblasts infected with attenuated varicella-zoster virus was performed. The laser plume was collected for polymerase chain reaction analysis and viral culture. RESULTS: While viral DNA was detected in the material trapped from the laser plume, live virus could not be demonstrated to have survived ablation. CONCLUSIONS: Attenuated varicella-zoster virus does not seem to survive excimer laser ablation. However, we recommend the use of safety precautions such as wearing a mask during the procedure. Further research is necessary to determine if other viruses could possibly remain infectious despite exposure to excimer laser radiation.

DNA, Viral↗
PubMed1996

Applications of the bacteriocin, nisin.

Nisin was first introduced commercially as a food preservative in the UK approximately 30 years ago. First established use was as a preservative in processed cheese products and since then numerous other applications in foods and beverages have been identified. It is currently recognised as a safe food preservative in approximately 50 countries. The established uses of nisin as a preservative in processed cheese, various pasteurised dairy products, and canned vegetables will be briefly reviewed. More recent applications of nisin include its use as a preservative in high moisture, hot baked flour products (crumpets) and pasteurised liquid egg. Renewed interest is evident in the use of nisin in natural cheese production. Considerable research has been carried out on the antilisterial properties of nisin in foods and a number of applications have been proposed. Uses of nisin to control spoilage lactic acid bacteria have been identified in beer, wine, alcohol production and low pH foods such as salad dressings. Further developments of nisin are likely to include synergistic action of nisin with chelators and other bacteriocins, and its use as an adjunct in novel food processing technology such as higher pressure sterilisation and electroporation. Production of highly purified nisin preparations and enhancement by chelators has led to interest in the use of nisin for human ulcer therapy, and mastitis control in cattle.

Animals↗
PubMed1996

Outcome of transsphenoidal surgery for acromegaly using strict criteria for surgical cure.

OBJECTIVE: Previous studies of surgical treatment for acromegaly have used varied criteria for 'cure', but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer-term outcome for patients not offered further treatment when post-operative levels of GH < 5 mU/l were achieved. DESIGN: We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew's Hospital between 1985 and 1993. PATIENTS: One hundred consecutive patients (53 male, mean age 46 years, range 18-68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5-8 years) after operation. MEASUREMENTS: GH levels are represented as a mean value from a four-point day curve taken at 0830, 1300, 1700 and 1900 h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured. RESULTS: Post-operatively, 42% of patients achieved a mean GH level of < 5 mU/l. The success of surgery was related to the preoperative GH level; 65% of the patients with preoperative GH levels < 20 mU/l but only 18% of the patients with GH levels > 100 mU/l achieved post-operative GH values < 5 mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post-operative GH levels of < 5 mU/l. Of the 42 patients considered in remission post-operatively (mean GH < 5 mU/l), 32 were available for long-term follow-up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow-up of 3.8 years (range 0.5-8). There were no peri-operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post-operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted. CONCLUSIONS: The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post-operative GH < 5 mU/l are achieved.

Acromegaly↗
PubMed1993

The effect of a mouthrinse based on nisin, a bacteriocin, on developing plaque and gingivitis in beagle dogs.

The aim of this study was to evaluate the effect of nisin, an antimicrobial peptide, on the development of plaque and gingivitis in beagle dogs when compared with 0.12% chlorhexidine and a placebo. 16 female beagle dogs 1 year of age were brought to optimum gingival health by scaling, root planing and polishing. At the conclusion of the pretreatment phase, the dogs were divided into 4 groups for the application of the test agents and were placed on a plaque promoting diet of Purina Dog Chow softened with water. Test agents included 100 micrograms/ml nisin and 300 micrograms/ml nisin formulated in a vehicle containing 1 mM NaEDTA; negative control comprised of exactly the same formulation but omitting nisin; and 0.12% chlorhexidine as Peridex. Throughout the treatment period, formulations were applied 2x daily to premolar teeth in each quadrant for 1 min using a Monojet syringe. The development of plaque and gingivitis was monitored at 15, 27, 39, 53, 74 and 88 days during the treatment phase using standard measurements of gingival index, plaque index, stain index and bleeding to probing. Throughout the treatment phase, plaque accumulation increased in all groups, but the rate of plaque build-up was less in groups treated with either nisin or chlorhexidine formulations compared with the placebo treated group. The gingival index of dogs in all groups increased throughout the study period. However, from day 27 onward, the groups receiving nisin had lower gingival index scores than did the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Visual diagnosis of hematologic and oncologic diseases.

Cancer-related problems are seen frequently by the emergency physician. More difficult presentations are seen with premonitory symptoms, paraneoplastic syndromes, and nonspecific lesions. Dermatologic paraneoplastic syndromes are numerous, nonspecific, and consist of hamartomatous growths, texture changes, new hair growth, or changes in skin color. Alteration of skin color may be of practically any color, localized or diffuse, and of sudden or indolent onset. Hormone production by tumors may lead to acne, hirsutism, gynecomastia, or a cushingoid appearance. Pruritus may herald the onset of leukemia or lymphoma and be intolerable, as with erythroderma. All suspicious presentations require thorough investigation for underlying disease. Metastasis to skin is not common and implies a poor prognosis if seen. Most metastases are seen on the head and neck, anterior chest wall, and abdomen. Basal cell and squamous cell carcinomas commonly occur in sun-exposed areas. Basal cell is locally destructive, whereas squamous cell occasionally metastasizes to local lymph nodes. Malignant melanoma is the leading fatal illness originating in skin, with a dramatic rise in incidence. It is classically described as asymmetric with irregular borders, is elevated, and shows color variegation; however, melanoma may present atypically, particularly in non-whites. Kaposi's sarcoma lesions are well-demarcated, symmetric, smooth nodules that appear purplish-brown, particularly if below the knee (owing to venous stasis). The closely interrelated structures of the eye and orbit are easily disturbed, leading to the presenting symptoms of visual disturbances, exophthalmos, pain, and ocular motility disorders. Primary tumors are not unusual and may include retinoblastoma, rhabdomyosarcoma, and melanoma. Equally common are metastatic lesions, most commonly lung and breast carcinoma. An estimation of the malignancy of bony lesions can be made by assessing the zone of transition, periosteal reaction, and bone destruction. A malignant lesion will more likely have a broad zone of transition, irregular periosteal reaction, and moth-eaten or permeative destruction of trabeculae. Metastatic bone lesions primarily occur in sites of persistent red marrow: skull, ribs, vertebrae, pelvis, and proximal humerus and femur. Bony lesions can be blastic or lytic in nature. Solitary pulmonary nodules that have not grown for 2 years can be assumed to be benign. Calcification seen on plain films are a strong (but not absolute) indication of benignancy. Lesions that are greater than 3 to 4 cm in diameter, have irregular contours, are cavitated with thick walls, have multiple peripheral nodules, and have lack of calcification are more likely malignant.

Emergencies↗
PubMed1992

Evaluation of a nisin-based germicidal formulation on teat skin of live cows.

A purified preparation of the nontoxic antimicrobial peptide, nisin (AMBICIN N), was used in the formulation of a germicidal sanitizer suitable for use on cow teats. The germicidal activity of the formulation against mastitis pathogens was measured on teat skin of live cows. The nisin-based formulation gave a mean log reduction of 3.90 against Staphylococcus aureus and 4.22 log reduction against Escherichia coli after exposure for 1 min to the germicide. This activity was comparable with that exhibited by a 1% iodophor teat dip but was significantly greater than that exhibited by the .1 and .5% iodophors and by the .5% chlorhexidine digluconate teat dips. The nisin-based formulation showed little or no potential for skin irritation after multiple application to skin, but iodophor and chlorhexidine digluconate teat dips showed significant potential for skin irritation in comparable studies.

Animals↗
PubMed1986

Amino acid sequence of a basic Agkistrodon halys blomhoffii phospholipase A2. Possible role of NH2-terminal lysines in action on phospholipids of Escherichia coli.

A basic (pI = 10.2) phospholipase A2 of the venom of the snake Agkistrodon halys blomhoffii is one of a few phospholipases A2 capable of hydrolyzing the phospholipids of Escherichia coli killed by a bactericidal protein purified from human or rabbit neutrophil granules. We have shown that modification of as many as 4 mol of lysine per mole of the phospholipase A2, either by carbamylation or by reductive methylation [Forst, S., Weiss, J., & Elsbach, P. (1982) J. Biol. Chem. 257, 14055-14057], had no effect on catalytic activity toward extracted E. coli phospholipids or the phospholipids of autoclaved E. coli. In contrast, modification of 1 mol of lysine per mole of enzyme substantially reduced activity toward the phospholipids of E. coli killed by the neutrophil protein. To explore further the role of lysines in the function of this phospholipase A2, we determined the amino acid sequence of the enzyme and the incorporation of [14C]cyanate into individual lysines when, on average, 1 lysine per molecule of enzyme had been carbamylated. After incorporation of approximately 1 mol of [14C]cyanate per mole of protein, the phospholipase A2 was reduced, alkylated, and exhaustively carbamylated with unlabeled cyanate. The amino acid sequence was determined of the NH2-terminal 33 amino acids of the holoprotein and of peptides isolated after digestion with trypsin and Staphylococcus aureus V-8 protease. The protein contains 122 amino acid residues, 17 of which are lysines. The NH2-terminal region is unique among more than 30 phospholipases A2 previously sequenced because of its high content of basic residues (His-1, Arg-6, and Lys-7, -10, -11, and -15).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1985

Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids.

Glutathione reductase from trypanosomes and leishmanias, unlike glutathione reductase from other organisms, requires an unusual low molecular weight cofactor for activity. The cofactor was purified from the insect trypanosomatid Crithidia fasciculata and identified as a novel glutathione-spermidine conjugate, N1,N8-bis(L-gamma-glutamyl-L-hemicystinyl-glycyl)spermidine, for which the trivial name trypanothione is proposed. This discovery may open a new chemotherapeutic approach to trypanosomiasis and leishmaniasis.

Animals↗
PubMed1984

Proteins synthesized in medial hypothalamus and transported to midbrain in estrogen-treated female rats.

Results on the anatomy of ventromedial hypothalamic outputs, together with the temporal aspects of electrophysiological studies, predict that for reproductive behavior control sex steroids alter hypothalamic protein synthesis and transport of proteins to the dorsal midbrain. We have studied labeled proteins arriving in the dorsal midbrain after local microinjection of tritiated amino acids to the ventromedial hypothalamus. Estrogen treated and control ovariectomized female rats are significantly different in this respect, and in particular some proteins appear to be synthesized or transported in greater amounts in the estrogen treated animals. Physical characterization of these proteins and comparisons under a variety of endocrine conditions will suggest whether their synthesis could be part of the mechanism by which ovarian steroids affect behavior.

Amino Acids↗
PubMed1984

Thiol-disulfide interchange between cystine and N-2-mercaptoethyl-1, 3-diaminopropane as a potential treatment for cystinuria.

The radioprotective compound WR2721 is a thiophosphate, which, when administered orally, is activated at the acid pH of the stomach to its free thiol (MDP). The free thiol is a mucolytic compound which acts via the reduction of disulfide bonds of mucin molecules. An equimolar mixture of MDP and cysteine, in urine at pH 6.0 and 37 degrees C, when oxidized by molecular oxygen, preferentially forms the soluble mixed disulfide between MDP and cysteine. The disulfide cystine will undergo thiol-disulfide interchange with MDP; as a result, cystine crystals are effectively dissolved. Moreover, in the presence of catalytic amounts of free thiol, the disulfide of MDP will undergo thiol-disulfide interchange with cystine to dissolve cystine crystals. The mixed disulfide of MDP with cysteine is soluble in urine at pH 6.0 and 37 degrees C to at least 100 mg/ml. Chromatographic procedures which permit the analysis of MDP and its mixed disulfide derivatives as MDP-sulfonic acid are described. By these procedures, it was demonstrated that 20% of a single oral dose of WR2721 was excreted as MDP derivatives in the urine of normal volunteers. These procedures will permit the evaluation of WR2721 in the treatment of cystinuria.

Amifostine↗
PubMed1984

The effect of dietary protein on cystine excretion in patients with cystinuria.

Seven patients with homozygous cystinuria were studied on a metabolic ward to determine the effect of dietary manipulation on urinary cystine excretion. Isocaloric diets were calculated based on body weight and activity. Balance studies were performed for 5 days on a low protein diet (9.4 +/- 1.0% total calories) with equal amounts of animal and plant protein sources and an additional 5 days on a high protein (27 +/- 3.0% of total calories) with 70% animal protein. A significant (p less than 0.01) decrease in the excretion of 1/2-cystine, histidine, 3-methylhistidine, 1-methylhistidine, lysine, and ornithine plus arginine occurred on the low protein diet. The mean excretion of 1/2-cystine on the high protein diet was 6.13 +/- 1.48 mMoles per 24 hours which decreased to 4.89 +/- 1.06 mMoles per 24 hours on the low protein diet (p less than 0.001). Thirty seven percent of urine collections during the study were less than 2 liters/24 hours despite the fact that patients were encouraged to drink enough fluid to make 3 liters of urine/24 hours. For patients whose customary diet is high in animal protein, a more vegetarian diet may significantly reduce urinary cystine excretion. Cystine excretion in patients with cystinuria may be significantly different from day to day if animal protein consumption is variable.

Adolescent↗
PubMed1983

Interaction of ribonuclease A with estrogen receptor from rat mammary tumor MTW9.

Incubation of crude estrogen receptor preparations from mammary tumor cytosol with RNase A increases the sedimentation coefficient of the receptor from 9.7 S to 10.4 S. The effect is not obtained with other low molecular weight basic proteins (lysozyme, cytochrome c, or histone H2B). Nonenzymically active RNase A derivatives such as performic acid oxidized RNase A, fully reductively methylated RNase A, carboxymethyl-His-119-RNase A, and RNase S-protein were ineffective. RNase T1, an acidic endoribonuclease, was also without effect. However, enzymically active RNase S', prepared from a mixture of RNase S-protein and S-peptide, shifted the sedimentation to 10.4 S. The increased sedimentation is not accompanied by a change in the Stokes radius of the receptor (74 A) or buoyant density in metrizamide (1.24 g/ml). The effect of RNase A on the sedimentation of the receptor can be reversed by subsequent incubation with human placental RNase inhibitor or with rabbit anti-RNase A antibodies. Direct interaction was shown by chromatography of the receptor on RNase A Sepharose. Thus, the shift in sedimentation results from binding of RNase A to the receptor and, although this requires that the enzyme active site be available, enzymic activity is not responsible for the effect. The interaction of RNase A with the receptor occurs at low ionic strength; it does not occur at elevated ionic strength or after activation of the receptor by precipitation with ammonium sulfate.

Animals↗
PubMed1982

Identification of lysine residues in the binding domain of ribonuclease A for the RNase inhibitor from human placenta.

Amidination of the available lysine residues of the complex between RNase A and human placental RNase inhibitor has been performed with methyl acetimidate; the conditions of the derivatization preserve the complex functionally intact. Resistance of epsilon-acetimidyllysine residues to hydrolysis by trypsin allowed, after peptide mapping, the identification of lysine residues 7, 31, 41, 61, and 91 as those which were fully protected by the inhibitor from amidination. Lysine residue 37 was partially protected from amidination. In the presence of poly(A), lysine residues 41 and 61 of RNase A were fully protected from amidination, while lysine residues 7, 31, 37, 91, and 104 were only partially protected; the enzyme retained full activity. The results permit identification of lysine residues located in the binding domain of RNase A for the inhibitor. This region is not identical with, but does overlap, the binding domain for poly(A).

Amino Acids↗