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Biomedical subjects

K Williams

Publications and source records attributed to K Williams.

At least 397 records · Page 22Linked to original sources

Bone marrow transplantation for constitutional pure red cell aplasia.

Constitutional pure red cell aplasia (CPRCA) is a syndrome of failed erythropoiesis usually diagnosed within the first year of life. Four patients with CPRCA received transplants with marrow from their HLA-identical, mixed lymphocyte culture-nonreactive siblings. All patients were resistant to corticosteroid therapy and were dependent on regular red cell transfusions for at least 5 years. Three patients were conditioned with procarbazine, antithymocyte globulin, cyclophosphamide, and busulfan, and one was conditioned with antithymocyte serum, cyclophosphamide, and busulfan. Three patients promptly had successful engraftments with establishment of donor hematopoiesis. One patient initially rejected his graft but received a successful retransplant. All patients are currently alive with Karnofsky performance scores of 100 and normal erythropoiesis of donor origin. Despite a history of multiple transfusions, bone marrow transplantation is a potentially curative therapy for patients with CPRCA.

Adolescent↗

Characterization of antigen 117. A developmentally regulated cell surface glycoprotein of Dictyostelium discoideum.

Antigen 117 is involved in the process of intercellular cohesion in Dictyostelium discoideum (Brodie, C., Klein, C., and Swierkosz, J. Cell 32, 1115-1123 (1983]. The antigen was shown to arise from a 62,000-64,000-dalton precursor. The mature antigen consists of two forms of molecular weights, 69,000 and 72,000. These forms are glycosylated, phosphorylated, acylated, and sulfated. Developmental changes in the cellular and cell surface levels of the antigen reflect changes in its rate of synthesis. All aggregating cells express antigen 117 on their surfaces. Antigen 117 then disappears from the surface of all cells when tip formation occurs. The antigen is re-expressed briefly again on cells undergoing culmination.

Antibodies, Monoclonal↗

Purification and characterization of pyruvate: ferredoxin oxidoreductase from the anaerobic protozoon Trichomonas vaginalis.

The pyruvate: ferredoxin oxidoreductase from the anaerobic protozoon Trichomonas vaginalis is an extrinsic protein bound to the hydrogenosomal membrane. It has been solubilized and purified to homogeneity, principally by salting-out chromatography on Sepharose 4B. Low recoveries of active enzyme were caused by inactivation by O2 and the irreversible loss of thiamin pyrophosphate. It is a dimeric enzyme of overall Mr 240,000 and subunit Mr 120,000. The enzyme contains, per mol of dimer, 7.3 +/- 0.3 mol of iron and 5.9 +/- 0.9 mol of acid-labile sulphur, suggesting the presence of two [4Fe-4S] centres, and 0.47 mol of thiamin pyrophosphate. The absorption spectrum of the enzyme is characteristic of a non-haem iron protein. The pyruvate: ferredoxin oxidoreductase from T. vaginalis is therefore broadly similar to the 2-oxo acid: ferredoxin (flavodoxin) oxidoreductases purified from bacterial sources, except that it is membrane-bound.

Amino Acids↗

Alterations in beta-adrenoceptor number and catecholamine content of chick atria after reversible sympathetic denervation with 6-hydroxydopamine.

1. The characteristics of [3H]-dihydroalprenolol (DHA) binding were determined in atria from untreated chicks. [3H]-DHA binding to atrium homogenates was rapid (k1 = 8.52 X 10(8) l mol-1 min-1), reversible (k-1 = 0.47 min-1), saturable, and of high affinity (KD = 0.6-1.0 nmol/l). Isoprenaline competed for specific [3H]-DHA binding in a stereoselective manner; IC50 values (mumol/l) were: (-)isoprenaline 0.12, (+)isoprenaline 4.7. 2. The number of [3H]-DHA binding sites and catecholamine content of left and right atria were examined after injection of chicks with a single dose of 6-hydroxydopamine hydrobromide (100 mg/kg). There were transient increases in the number of [3H]-DHA binding sites in both the left and the right atrium after 6-OHDA treatment. These increases were quicker in onset and in offset in the right atrium than in the left atrium. [3H]-DHA binding was significantly increased in the left atrium at 5 and 7 days, and in the right atrium at 3 and 5 days after 6-OHDA injection. 3. Saturation binding isotherms indicated that the increase in [3H]-DHA binding was due to an increase in beta-adrenoceptor number with no change in affinity for [3H]-DHA. 4. Twenty four hours after 6-OHDA treatment there was a significant (80%) decrease in noradrenaline content of left and of right atria. 5. The decrease in noradrenaline content was reversible, noradrenaline levels returning to 55% of control in left atrium and to 71% of control in right atrium by 21 days after 6-OHDA treatment. These changes are consistent with reversible sympathetic denervation of the atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Factors influencing susceptibility to meningococcal disease during an epidemic in The Gambia, West Africa.

A study was made of factors that influenced susceptibility to group A meningococcal disease during an epidemic that affected The Gambia, West Africa during the dry season of 1982-83. No explanations were found for the distribution of cases between villages or within affected villages. Socio-economic status, crowding, nutrition and previous exposure to meningococcal disease all appeared to be unimportant. Examination of serum samples obtained before the outbreak from a few children who subsequently became patients and from an equal number of age-matched controls from the same village showed a higher mean serum IgA value in children who became patients than in controls. There were not, however, any significant differences found in the concentrations of IgG, IgM, complement or meningococcal antibody between the two groups. Four children who developed culture-proven group A meningococcal disease had raised titres of bactericidal antibody to the epidemic strain 2-3 months before their illnesses. Our findings suggest that some important risk factors for group A meningococcal disease remain to be identified.

Adolescent↗

Demonic possession and mental disorder in medieval and early modern Europe.

Western European belief in demonic possession as a cause of mental disorder has been traced through the medieval and early modern periods. Generally it appears that the range of disorders attributed to demonic possession has gradually narrowed. In any period, however, there seem to have been marked individual and cultural differences in outlook; some of these differences are still evident today in the survival of belief in demonic possession in pentecostal sects.

Christianity↗

Comparison of alcohol shock enrichment and selective enrichment for the isolation of Clostridium difficile.

Two enrichment methods were compared for their ability to recover Clostridium difficile from stool samples. One method used selective enrichment in an antibiotic-containing broth followed by detection with a latex particle agglutination (LPA) reagent. The other used enrichment in a non-selective broth following treatment of the specimen with alcohol. With clinical specimens enrichment culture was significantly more successful at detecting C. difficile than direct plating. Alcohol shock enrichment was twice as effective as direct culture, while selective broth enrichment was three times more effective. The use of LPA for screening selective enrichment broths for C. difficile should prove a cost-effective measure as only positive broths (about 20%) require subculture for confirmation.

Bacteriological Techniques↗

Alternative processing during development of a macronuclear chromosome family in Oxytricha fallax.

Macronuclear chromosomes in Oxytricha fallax, a hypotrichous ciliate, are very short. They often belong to small families of cross-hybridizing chromosomes of two or three different sizes. For example, the 81-MAC family consists of three sizes of macronuclear chromosomes (4.9, 2.9, and 1.6 kbp) (Cartinhour and Herrick 1984). We show that the family actually consists of two closely related sets of three each and that the two sets are independently created by alternative processing of two separate precursor (micronuclear) versions. Chromosomes of a set share a common 1.6-kbp region, which contains a transcribed gene coding for a 25-kD protein. Different-sized macronuclear chromosomes of a set result from alternative choices of positions for telomere formation. All six members of the family are reproducibly generated in each developing macronucleus, and their copy numbers are stably maintained during vegetative replication of the macronucleus (Herrick et al. 1987). Here we argue for the existence of three distinct copy control elements in the 81-MAC family chromosomes. A model is discussed in which, following polytenization of the micronuclear chromosomes, different chromatids are processed differently, and, subsequently, replication-competent macronuclear chromosome products are amplified under the influence of the vegetative copy control elements.

Amino Acid Sequence↗

Randomized prospective study of ceftazidime versus ceftazidime plus cephalothin in empiric treatment of febrile episodes in severely neutropenic patients.

In a prospective randomized study, ceftazidime monotherapy was compared with a combination of ceftazidime plus cephalothin in 102 febrile neutropenic patients. Thirty bacteriologically documented infections, of which 23 were bacteremias, in 48 clinically assessable patients were treated with ceftazidime alone. Twenty-four bacteriologically proven infections, of which 18 were bacteremias, in 42 clinically assessable patients were treated with a combination of ceftazidime and cephalothin. The clinical response rates in assessable patients were 77% for ceftazidime monotherapy and 88% for the combination. The bacteriological clearance rate was 70% for ceftazidime monotherapy and 79% for the combination. Efficacy against gram-negative pathogens appeared to be excellent, with 93% clearance for ceftazidime monotherapy and 100% clearance for the combination. The bacteriological clearance of gram-positive infections was only 60% for both regimens, with failures mainly due to Streptococcus faecalis and Streptococcus sanguis, which are primarily resistant to both ceftazidime and cephalothin. After addition of vancomycin to those infections which did not respond to empiric therapy, bacteriological clearance rates of 94% (ceftazidime plus vancomycin) and 90% (ceftazidime and cephalothin plus vancomycin) were achieved. Three superinfections were registered in the ceftazidime group and two were seen in the combination group. Other adverse effects of ceftazidime were minimal and were not enhanced by combination with cephalothin. It is concluded that ceftazidime is an effective drug for the empiric treatment of febrile neutropenic patients, especially if one is prepared to modify therapy if resistant gram-positive strains or mycotic infections are encountered. Neither the clinical nor bacteriological cure rates could be substantially improved by adding cephalothin to ceftazidime in initial empiric treatment of febrile neutropenic patients.

Adolescent↗

Accelerated transfer of cholesteryl esters in dyslipidemic plasma. Role of cholesteryl ester transfer protein.

Plasma cholesteryl esters, synthesized in the high density lipoproteins (HDL), may be transferred to other lipoproteins by a cholesteryl ester transfer protein (CETP). We found a twofold increase in mass transfer of cholesteryl ester from HDL to apoB-containing lipoproteins in incubated hypercholesterolemic rabbit plasma compared with control. There was a two- to fourfold increase in the activity of CETP, measured in an isotopic assay in hypercholesterolemic plasma. A CETP-like molecule was isolated in increased amounts from hypercholesterolemic plasma. Incubated plasma from four dysbetalipoproteinemic subjects also showed an increase (threefold) in cholesteryl ester mass transfer, compared with normolipidemic controls. There was a twofold increase in the activity of CETP, assayed in whole or lipoprotein-free plasma. Thus, there is increased transfer of cholesteryl esters from HDL to potentially atherogenic apoB-containing lipoproteins in dyslipidemic rabbit and human plasma. The enhanced transfer results in part from increased activity of CETP, possibly reflecting an increase in CETP mass.

Animals↗

Specific cross-gender behaviour in boyhood and later homosexual orientation.

Data from a group of males aged 13 to 23, who as children exhibited extensive cross-gender behaviour, was analysed. In boyhood they frequently played with dress-up dolls, role-played as females, dressed in girls' clothes, stated the wish to be girls, primarily had girls as friends, and avoided rough-and-tumble play. The majority of the group evolved a bisexual or homosexual orientation; two types of behaviour, boyhood doll play and female role-playing, were found to be associated with later homosexual orientation. The findings suggest developmental associations between specific types of boyhood cross-gender behaviour and the objects of later sexual arousal.

Child Behavior↗

Effects of noradrenergic denervation on alpha-1 adrenoceptors and receptor-stimulated contraction of chick expansor secundariorum muscle.

Alpha-1 adrenoceptors were identified in the chick expansor secundariorum (ESM) smooth muscle by ligand binding (using [3H]prazosin) and organ bath techniques. We examined the effects of both reversible (6-hydroxydopamine-induced) and irreversible (surgical) noradrenergic denervation on alpha-1 adrenoceptors in the ESM. We also measured, in vitro, muscle contraction stimulated by the alpha-1 adrenoceptor agonist methoxamine and by 5-hydroxytryptamine. After both surgical and chemical denervation there were decreases in the number of [3H] prazosin binding sites in the ESM. After reversible denervation the decrease in receptor number persisted during a period in which there was extensive reinnervation of the muscle. At a time (7 days after injection) when the ESM was partially reinnervated the maximum methoxamine-stimulated response, but not that of 5-hydroxytryptamine, was reduced. After surgical (but not chemical) denervation there were increases in both protein content and wet weight of the muscle. However, at 7 days after denervation, these effects alone could not account for the observed decrease in receptor number. A small increase in sensitivity (1.4-fold) to methoxamine and a much larger increase in sensitivity (4.5-fold) to 5-hydroxytryptamine developed after surgical denervation but there appeared to be nonspecific decreases in maximum responses to the agonists. It is concluded that both surgical and chemical denervation produced a decrease in alpha-1 adrenoceptor number in the ESM; this may have contributed to the decrease in maximum contractile response. After surgical denervation a nonspecific supersensitivity developed in the ESM; it may be that a nonspecific contribution to methoxamine-stimulated responses was less apparent due to the loss of alpha-1 adrenoceptors.

Animals↗