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Biomedical subjects

B J Williams

Publications and source records attributed to B J Williams.

At least 73 records · Page 4Linked to original sources
PubMed1991

Correlation of Histoplasma capsulatum polysaccharide antigen with the severity of infection in murine histoplasmosis.

We sought to determine if Histoplasma capsulatum polysaccharide antigen (HPA) levels correlate with the extent of infection in murine of histoplasmosis. Separate groups of mice were inoculated intratracheally with varying numbers of H. capsulatum yeast cells. After 1 week, HPA levels and fungal burden (quantitative culture of lung and spleen and histopathologic stain of lung) were determined in lung and spleen, and HPA levels in serum. HPA levels, cultures and histopathological stain results of lung and spleen tissue showed a direct correlation with increasing inoculum size. HPA levels in serum also correlated with the size of inoculum. H. capsulatum antigen in lung correlated with silver stain scores of lung tissue, (R = 0.948, P less than 0.001) and with quantitative culture scores of lung, (R = 0.929, P less than 0.001). HPA levels in spleen tissue also correlated with spleen culture scores, (R = 0.724, P less than 0.001). These results indicate that determination of HPA level in serum and tissue may be a useful test in evaluating the severity of diseases as well as efficacy of antifungal therapy in histoplasmosis.

Animals↗
PubMed1991

Kynurenic acid derivatives. Structure-activity relationships for excitatory amino acid antagonism and identification of potent and selective antagonists at the glycine site on the N-methyl-D-aspartate receptor.

Derivatives of the nonselective excitatory amino acid antagonist kynurenic acid (4-oxo-1,4-dihydroquinoline-2-carboxylic acid, 1) have been synthesized and evaluated for in vitro antagonist activity at the excitatory amino acid receptors sensitive to N-methyl-D-aspartic acid (NMDA), quisqualic acid (QUIS or AMPA), and kainic acid (KA). Introduction of substituents at the 5-, 7-, and 5,7-positions resulted in analogues having selective NMDA antagonist action, as a result of blockade of the glycine modulatory (or coagonist) site on the NMDA receptor. Regression analysis suggested a requirement for optimally sized, hydrophobic 5- and 7-substituents, with bulk tolerance being greater at the 5-position. Optimization led to the 5-iodo-7-chloro derivative (53), which is the most potent and selective glycine/NMDA antagonist to date (IC50 vs [3H]glycine binding, 32 nM; IC50's for other excitatory amino acid receptor sites, greater than 100 microM). Substitution of 1 at the 6-position resulted in compounds having selective non-NMDA antagonism and 8-substituted compounds were inactive at all receptors. The retention of glycine/NMDA antagonist activity in heterocyclic ring modified analogues, such as the oxanilide 69 and the 2-carboxybenzimidazole 70, suggests that the 4-oxo tautomer of 1 and its derivatives is required for activity. Structurally related quinoxaline-2,3-diones are also glycine/NMDA antagonists, but are not selective and are less potent than the 1 derivatives, and additionally show different structure-activity requirements for aromatic ring substitution. On the basis of these results, a model accounting for glycine receptor binding of the 1 derived antagonists is proposed, comprising (a) size-limited, hydrophobic binding of the benzene ring, (b) hydrogen-bond acceptance by the 4-oxo group, (c) hydrogen-bond donation by the 1-amino group, and (d) a Coulombic attraction of the 2-carboxylate. The model can also account for the binding of quinoxaline-2,3-diones, quinoxalic acids, and 2-carboxybenzimidazoles.

Animals↗
PubMed1991

Subperiosteal abscesses of the orbit due to sinusitis in childhood.

This paper reports 16 cases of subperiosteal abscesses of the orbit due to acute sinusitis in childhood. They comprise 12.4% of 129 patients presenting with an 'acute orbit'. Acute ethmoidal sinusitis was the predominant cause. The typical clinical features, as well as CT scanning of the paranasal sinuses, orbit and brain, should assist in early diagnosis. If possible, the subperiosteal abscess and sinuses should be drained before loss of visual acuity or intracranial complications occur. Streptococcus milleri was the pathogen most commonly cultured. One patient in this series had intracranial complications, but no other patients had major complications and there were no deaths.

Abscess↗
PubMed1991

Pharmacological specificity of novel, synthetic, cyclic peptides as antagonists at tachykinin receptors.

1. The interaction at tachykinin receptors of a series of novel cyclic hexapeptides has been examined by use of radioligand binding assays (NK1 and NK3 sites in rat cortex, NK2 sites in hamster urinary bladder) and functional pharmacological assays (guinea-pig ileum, rat vas deferens and rat portal vein for NK1, NK2 and NK3 receptors, respectively). 2. The compounds cyclo(GlnTrpPhe(R)Gly[ANC-2]LeuMet) (L-659,837) and cyclo(GlnTrpPheGly-LeuMet) (L-659,877) were powerful and selective displacers of NK2 binding (pIC50 6.9 and 8.0, respectively), and were competitive antagonists of responses to stimulation of NK2 receptors in rat vas deferens (pKB for antagonism of responses to eledoisin 6.7 and 8.1, respectively). Responses in the NK1 and NK3 pharmacological assays were blocked only weakly, if at all. 3. In the longitudinal muscle of the small intestine of the rat, responses to stimulation of the putative NK2 receptor by eledoisin, neurokinin A or neurokinin B were antagonized by both cyclo(GlnTrpPhe(R)-Gly[ANC-2]LeuMet) and cyclo (GlnTrpPheGlyLeuMet) in a manner consistent with the presence in this tissue of a uniform population of receptors, indistinguishable from the NK2 receptor of the rat vas deferens. 4. The compounds cyclo(GlnTrpPheGlyLeuMet) and the lactam-containing analogue are among the most selective antagonists for the NK2 receptor that have been described; their availability should be of value in the characterization of the receptors mediating responses to tachykinins, and in elucidating the physiological functions of the tachykinin receptors.

Amino Acid Sequence↗
PubMed1991

The influence of egg sequence position on fertility, embryo viability, and embryo weight in broiler breeders.

A study was undertaken to determine whether fertility, early embryo viability, and the weight of the egg, shell, and embryo are influenced by the position of an egg in a laying sequence. One hundred and three Indian River broiler breeder hens were housed individually in cages at 21 wk of age. Beginning at 43 wk of age, each hen was inseminated once per week, with 50 microL of fresh undiluted pooled semen from Indian River broiler breeder males. Beginning at 45 wk of age, and for the following 45 days, all eggs laid were collected. Eggs were collected hourly for 8 h after "lights on" and a final daily collection was made 14 h after lights on. Each egg was classified as "first-of-sequence" or "subsequent". Eggs were weighed and placed in a forced-air incubator twice per week. After 168 h of incubation, the eggs were removed from the incubator, weighed and assessed for fertility and embryo viability status. The embryo was also weighed. Shell weight was recorded after 3 to 4 days of air drying. Egg weight was significantly greater in first-of-sequence compared with subsequent eggs. First-of-sequence eggs exhibited significantly smaller Day 7 embryos (on a percentage basis), lower shell weight (on a percentage basis), and significantly less egg weight loss during the 7 day incubation period (absolute and percentage basis) than did subsequent eggs on a sequence. Least squares (LS) means for fertility did not differ significantly between first (87.02%) and subsequent (89.56%) eggs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Raised vascular calcium in an animal model: effects on aortic function.

STUDY OBJECTIVE - The aim of the study was to develop an animal model to study the relationships between raised tissue calcium and vascular function. DESIGN - Ectopic calcification was developed in the animal model using chronic vitamin D2 intoxication, after which functional studies were performed in isolated superfused aortic rings. Results were compared with control preparations. EXPERIMENTAL ANIMALS - 160 female Sprague-Dawley rats weighing 200-225 g were randomly divided into experimental (vitamin D2 1 mg.d-1) and control (vehicle only) groups. MEASUREMENTS and RESULTS - Aortas from vitamin D treated animals had a higher calcium content than control aortas, without concomitant increases in cardiac calcium. Aortas with high calcium content were found to develop greater tension than control aortas when exposed to noradrenaline in the absence of extracellular calcium, but the tension maxima achieved in response to noradrenaline in calcium containing media or to high potassium depolarising solution were the same. The rate of development of contraction in response to noradrenaline was greater in aortas from the vitamin D treated animals than in controls. Isoprenaline and sodium nitroprusside produced less relaxation in the animal model aortas than in the controls. CONCLUSIONS - The results suggest that increased aortic calcium affects the response of the tissue to vasoactive agents. It appears that the additional vascular calcium may be stored in an agonist releasable pool, probably within the sarcoplasmic reticulum. The enlarged or newly developed pools appear to be refillable from the extracellular medium but not by intracellular reuptake of calcium, suggesting a bicompartmental model of intracellular calcium release and reuptake.

Animals↗
PubMed1990

Pharmacological characterization of tachykinin-stimulated inositol phospholipid hydrolysis in peripheral tissues.

1. Tachykinin-stimulated inositol phospholipid hydrolysis was examined in slices of rat parotid gland, hamster urinary bladder and guinea-pig ileum longitudinal muscle. 2. In the presence of lithium, substance P and other naturally-occurring and synthetic tachykinins induced large, dose-dependent increases in [3H]-inositol monophosphate accumulation. 3. In slices of rat parotid gland, [pGlu6,L-Pro9]SP(6-11) was considerably more potent in stimulating inositol phospholipid hydrolysis than [pGlu6,D-Pro9]SP(6-11). 4. In contrast, in slices of hamster urinary bladder, [pGlu6,D-Pro9]SP(6-11) exhibited greater potency in evoking inositol phospholipid breakdown than [pGlu6,L-Pro9]SP(6-11). 5. The differential selectivity of these C-terminal fragments of substance P suggests that they may be useful tools for distinguishing between NK1 and NK2 receptors. 6. L-659,837 and L-659,874 antagonized eledoisin-stimulated inositol phospholipid hydrolysis in slices of hamster urinary bladder. Neither compound significantly reduced substance-P evoked inositol phospholipid breakdown in slices of rat parotid gland, or senktide-induced inositol phospholipid hydrolysis in slices of guinea-pig ileum. 7. L-659,837 and L-659,874 had no effect on the atropine-sensitive, carbachol-stimulated inositol phospholipid hydrolysis in slices of rat parotid gland. 8. These data further support the notion that L-659,837 and L-659,874 are potent and selective NK2 receptor antagonists.

Animals↗
PubMed1988

Effect of prazosin on the cardiopulmonary response to dopamine in awake lambs: comparison with phentolamine and tolazoline.

Combination vasodilator and cardiotonic therapy may help infants with pulmonary vasospasm and low cardiac output. We previously have shown that the alpha 1- and alpha 2- blocking agents tolazoline and phentolamine, plus dopamine, improved cardiac output relative to dopamine alone, without changing pulmonary vascular resistance. To similarly test an agent with selective alpha 1-receptor blocking action, prazosin, we instrumented 6 newborn lambs to measure the pressure in the pulmonary artery, aorta and left atrium and cardiac output. After recovery, the lambs were studied while awake and breathing room air. The response to dopamine, at doses of 2.7, 27 and 270 micrograms/kg/min, was measured alone, and again on a different day after prazosin (1 mg/kg). Dopamine alone raised systemic, pulmonary and left atrial pressure, and systemic vascular resistance at high doses. Pulmonary vascular resistance did not change. Prazosin prevented the dopamine-induced systemic resistance increase and permitted cardiac output to rise relative to dopamine alone (p less than 0.0125), but barely blunted the dopamine-induced pulmonary pressure increase (p less than 0.005 vs. base in both groups). These results are similar to those previously found with tolazoline and phentolamine. Thus, all the tested alpha-blockers facilitate the cardiotonic effect of dopamine, but none ablates its pulmonary pressure effect.

Animals↗
PubMed1988

Influence of repeated upper airway obstruction on the arousal and cardiopulmonary response to upper airway obstruction in lambs.

Experiments were done on five lambs to determine if repeated obstruction of the upper airway influences the arousal and cardiopulmonary response to upper airway obstruction. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial hemoglobin oxygen saturation. A tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea. The animals were studied after a 3-day recovery period. During a study, a 5F balloon-tipped catheter was inserted into the tracheostomy tube so that air flow could be obstructed by inflating the balloon. The balloon was inflated each time the animal went to sleep for approximately 100 consecutive epochs (17 to 30 h) and the time to arousal and the arterial hemoglobin oxygen saturation at arousal were recorded. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred from both sleep states during upper airway obstruction but was delayed in active sleep compared to quiet sleep. The time to arousal and the decrease in arterial hemoglobin oxygen saturation were significantly increased with repeated upper airway obstruction only during active sleep. Inasmuch as it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death, studies to investigate the mechanisms of the state-specific changes in the arousal response to upper airway obstruction are warranted.

Airway Obstruction↗
PubMed1987

Senktide, a selective neurokinin B-like agonist, elicits serotonin-mediated behaviour following intracisternal administration in the mouse.

Behavioural responses to tachykinins were observed following intracisternal administration in mice. The synthetic NK-3 agonists senktide and L-363,851 caused behaviour typically associated with serotonergic stimulation, including head twitches, reciprocal forepaw treading and hindlimb splaying. Neurokinin B produced some features of the serotonin (5-HT) syndrome, while substance P, neurokinin A and eledoisin failed to elicit any such behaviours. Senktide-induced head twitches were prevented by pretreatment with the 5-HT2 antagonists ketanserin and ritanserin, while forepaw treading was attenuated by the 5-HT1 antagonists (-)-pindolol and methysergide. These data suggest that NK-3 agonists interact with central 5-HT mechanisms.

Animals↗
PubMed1987

Rates of evolution: is there a conflict between neo-darwinian evolutionary theory and the fossil record?

Neo-darwinian and population genetics theory assumes that the necessary and sufficient set of conditions for all genetic, therefore evolutionary, change has been identified. Punctuationalists have assumed the opposite and cite the fossil record as evidence for change too rapid to be explained in neo-darwinian theory. Data is given here to provide estimates of the rate of evolution in hominid fossils, in living populations, and of that rate which would qualify as punctuational in the hominid fossil record. Evolution in living populations is orders of magnitude greater than that found in the fossil record and far greater than necessary to create apparently instantaneous saltations in the fossil record. It is suggested that such saltations may not represent more rapid rates of evolution but, rather, the persistence of evolutionary change in a given direction for a longer than normal period.

Animals↗
PubMed1987

Effects of tachykinins on inositol phospholipid hydrolysis in slices of hamster urinary bladder.

Tachykinin-stimulated inositol phospholipid hydrolysis was examined in slices of hamster urinary bladder. In the presence of lithium, to inhibit inositol monophosphatase activity, substance P, eledoisin and related tachykinins induced large, dose-dependent increases in [3H]-inositol monophosphate accumulation. The responses to substance P and eledoisin were not antagonized by the cholinoceptor antagonist, atropine. The rank order of potency for various tachykinins was kassinin greater than neurokinin A greater than neurokinin B greater than eledoisin greater than physaelamin greater than substance P greater than substance P methyl ester. The synthetic analogue [p-Glu6, D-Pro9]SP (6-11) was considerably more potent than its L-prolyl stereoisomer at stimulating inositol phospholipid hydrolysis. These results suggest that in the hamster urinary bladder, tachykinin-induced inositol phospholipid breakdown is mediated via tachykinin receptors of the SP-E type, as opposed to the SP-P type.

Animals↗
PubMed1987

Sonographic detection of neonatal umbilical-artery thrombosis: clinical correlation.

Eighty-one neonates were prospectively studied by sonography of the abdomen to determine the frequency, risk factors, clinical symptoms, complications, and natural history of aortic thrombosis seen in conjunction with the use of umbilical-artery catheters. Twenty-six percent of neonates developed sonographically detectable thrombosis. Twenty-nine percent of the neonates with thrombosis were asymptomatic, and an additional 24% had hematuria (diagnosed by dipstick) as their only clinical finding. Significant risk factors associated with aortic thrombosis were calcium in the umbilical-artery-catheter infusate, placement of the catheter for any length of time above the renal arteries, and low birth weight. Physical examination did not reliably predict aortic thrombosis, and asymptomatic thrombosis was more frequent than previously recognized.

Aorta, Abdominal↗
PubMed1986

Multiple tachykinin binding sites in peripheral tissues and in brain.

Tachykinin binding sites in guinea pig urinary bladder (GPUB), rat salivary gland (RSG), hamster urinary bladder (HUB), rat vas deferens (RVD) and rat cerebral cortex (RCC) were compared using 125I-Bolton Hunter conjugates of substance P (125I-BHSP), eledoisin (125I-BHE) and neurokinin A (125I-BHNKA). In typical SP-P tissues (GPUB, RSG) and in RCC, SP was the most potent displacer of 125I-BHSP and [Glp6,D-Pro9]-SP(6-11) was 90 times less active than [Glp6,L-Pro9]-SP(6-11) while SP methyl ester (SPOMe) was 5-10 times more active than the Bolton Hunter conjugate of SPOMe (I-BHSPOMe). On the other hand, in typical SP-E tissues (HUB, RVD), neurokinin A was most potent in displacing 125I-BHE and [Glp6,D-Pro9]-SP(6-11) was over 300 times more active than [Glp6,L-Pro9]-SP(6-11) while SPOMe was 160 times less active than I-BHSPOMe. In rat cerebral cortex, the rank order of potency of tachykinins and related analogues in displacing 125I-BHE was distinct from that of peripheral SP-E sites, with neurokinin B being the most potent displacer, and SPOMe was over 1,000 times more active than I-BHSPOMe; 125I-BHE binding sites in CNS may represent a third category of tachykinin receptor, designated SP-N.

Animals↗
PubMed1985

The comparative distribution of [Lys8-Asn9]-neurotensin8-13-like immunoreactivity in chicken and rat tissues.

The presence of [Lys8-Asn9]-neurotensin8-13-like immunoreactivity was studied by radioimmunoassay in chicken and rat tissues. In the chicken, [Lys8-Asn9]-neurotensin8-13-like immunoreactivity showed a wide distribution throughout the central nervous system and the gastrointestinal tract, and the immunoreactive material co-eluted with the synthetic peptide on reverse-phase high performance liquid chromatography. In the rat, [Lys8-Asn9]-neurotensin8-13-like immunoreactivity was widely distributed when 0.1 M HCl was used as the extraction procedure. However, the immunoreactive material did not co-elute with the synthetic peptide on reverse-phase high performance liquid chromatography; moreover, the addition of the aspartic proteinase inhibitor pepstatin to the extraction medium resulted in a large reduction in the levels of [Lys8-Asn9]-neurotensin8-13-like immunoreactivity and no immunoreactive material could be detected when the tissues were extracted using acetone/HCl. The present results therefore indicate that [Lys8-Asn9]-neurotensin8-13-like immunoreactivity is not present in rat tissues. That which was detected resulted from an extraction artefact.

Animals↗