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Biomedical subjects

T D Williams

Publications and source records attributed to T D Williams.

180 records · Page 10Linked to original sources
PubMed1970

Serum Neutralization Anti-IgG Test for Psittacosis.

Levels of antibodies in sera from patients with diagnoses of subclinical or established psittacosis infections were determined by the serum neutralization anti-IgG test and by conventional tests. Relatively high levels of serum neutralizing anti-bodies were detected in tests in which anti-IgG was used, whereas conventional tests disclosed only marginal levels of antibody. Use of the serum neutralization anti-IgG test in conjunction with the fluorescent cell-counting technique permitted serum antibody determinations within 24 hr.

Journal Article↗
PubMed1968

Responses evoked in the cerebellar cortex by stimulation of the caudate nucleus in the cat.

1. Responses evoked in the cerebellar cortex following stimulation of caudate nucleus are described.2. The evoked responses recorded from the surface of the cerebellar cortex were found to be of two types, one with a short (4-6 msec) latency and one with a longer (12-17 msec) latency.3. The short latency response was maximal in the lobulus simplex, the longer latency response was maximal in paramedian lobule.4. Following lesions in the inferior olive the longer latency response was absent.5. Recordings from within the cerebellar cortex showed that the short latency response was uniformly distributed throughout the grey matter, the longer latency response was maximal in the region of the Purkinje cell bodies.6. It was concluded that the short latency response was due to activation via the mossy fibres and the longer latency response to activation via the climbing fibres.7. It was found that responses could be evoked in the cerebellum following stimulation of only the latero-ventral part of the caudate nucleus; stimulation of the rest of the nucleus caused no response in the cerebellum. This division of the caudate nucleus into two parts is similar to the subdivision of the caudate nucleus made by other workers using different criteria.

Animals↗
PubMed1967

Responses of single units in the inferior olive to stimulation of the limb nerves, peripheral skin receptors, cerebellum, caudate nucleus and motor cortex.

1. Extra- and intracellular responses of single units in the inferior olive following stimulation of the cerebellum, limb nerves, skin receptors, the caudate nucleus and cerebral cortex have been described.2. Responses following cerebellar stimulation were assumed to be antidromic spikes when they occurred after a latency of less than 4 msec and followed stimulus frequencies greater than 220/sec. Other responses with longer latencies were thought to be transynaptic. Evidence for recurrent inhibition of the Renshaw type is given.3. Following limb nerve stimulation two types of units have been observed; units responding after a short latency and to stimulation of one limb only and units responding with a long latency following stimulation of one or more of the limbs.4. Units responding to stimulation of the limb nerve after a short latency could often be excited by hair movement and/or light touch on the pads. Other units were excited by pinching and others could not be excited by a physiological stimulus. The receptive field of these units was small and there was no evidence of fringe inhibition.5. Most units observed represented the contralateral forelimb but there was a significant number of units representing the ipsilateral limbs.6. The caudato-olivary pathway has been shown to be excitatory. Short latency limb units do not receive afferents from the caudate nucleus.7. Afferents from the motor cortex excite units in the inferior olive. A remarkable correlation of latencies of responses from both the cerebral cortex and the limbs on to individual units has been described.8. The results suggest a complex organization of neurones within the inferior olive. A possible plan of the organization of neurones is given and discussed.

Animals↗
PubMed1967

The response of single units in the caudate nucleus to peripheral stimulation.

1. Extra- and intracellular recordings have been made of single units in the caudate nucleus of the cat, anaesthetized with alpha chloralose.2. Pentobarbitone was shown to depress the spontaneous activity and responses of units in the caudate nucleus.3. Spontaneous activity of units usually took the form of single spikes or bursts of up to four spikes occurring every 100-300 msec.4. The response to electrical stimulation of limb nerves was a burst of 1-4 spikes after a latency of about 30 msec. Convergence from all four limbs on to single units was observed. It is shown that muscle afferents do not cause these responses.5. Post stimulus histograms of spontaneously active units show, following stimulation of the limb nerves, recurring cycles of excitation and inhibition at a rate of 3-4 c/s and lasting for several seconds. It is suggested that each stimulus synchronizes the normally rhythmic spontaneous activity.6. Similar responses have been obtained following stimulation by clicks and flashes of light.7. Stimulation of the ipsilateral cerebral cortex gave excitatory and inhibitory responses similar to those described above.8. Possible mechanisms for these responses and their significance are discussed.

Animals↗
PubMedDate not supplied

The cytochrome P450 1A gene (CYP1A) from European flounder (Platichthys flesus), analysis of regulatory regions and development of a dual luciferase reporter gene system.

Concensus primers designed to CYP1A-conserved regions were used to amplify a 1.3 kb probe from flounder genomic DNA via polymerase chain reaction (PCR). A 14-kb clone was isolated from a flounder genomic library constructed in lambda FIXII. Of this clone, 8 kb was sequenced, including 3 kb of upstream sequence. The predicted amino acid sequence showed closest similarity to plaice CYP1A1 (98%). Gene structure conformed to the seven exons and six introns common to previous CYP1A sequences, but intron lengths were not conserved. Concensus sequences corresponding to xenobiotic and other response elements as well as TATA, CAAT and GC boxes were identified. Upstream sequence (3.5 kb) including the first exon and intron up to the putative start codon were amplified via PCR and inserted upstream of the luciferase gene in a pGL3 reporter gene construct. The HepG2 mammalian hepatoma cell line was transiently co-transfected with the flounder CYP1A reporter gene construct and the pRL-CMV internal control construct. The maximal induction upon exposure to 100 nM 3-MC was 4.4-fold in comparison with carrier-treated cells. Use of deletion constructs resulted in loss of inducibility.

Animals↗
PubMedDate not supplied

Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension.

Thiazolidinediones are a new class of antidiabetic agent that improve insulin sensitivity and reduce plasma glucose and blood pressure in subjects with type 2 diabetes. Although these agents can bind and activate an orphan nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), there is no direct evidence to conclusively implicate this receptor in the regulation of mammalian glucose homeostasis. Here we report two different heterozygous mutations in the ligand-binding domain of PPARgamma in three subjects with severe insulin resistance. In the PPARgamma crystal structure, the mutations destabilize helix 12 which mediates transactivation. Consistent with this, both receptor mutants are markedly transcriptionally impaired and, moreover, are able to inhibit the action of coexpressed wild-type PPARgamma in a dominant negative manner. In addition to insulin resistance, all three subjects developed type 2 diabetes mellitus and hypertension at an unusually early age. Our findings represent the first germline loss-of-function mutations in PPARgamma and provide compelling genetic evidence that this receptor is important in the control of insulin sensitivity, glucose homeostasis and blood pressure in man.

Adult↗
PubMedDate not supplied

Food intake, locomotor activity, and egg laying in zebra finches: contributions to reproductive energy demand?

We tested two alternative hypotheses: (1) that energy costs of egg production in a small, short-lived passerine, the zebra finch (Taeniopygia guttata), are additive to the animal's total energy budget and are met by an increase in food intake or (2) that birds compensate for the energy costs of egg production by reducing energy expended on locomotor activity, thus, reallocating, but not increasing, their total energy budget. Breeding pairs of zebra finches had 8% lower daily food intake than nonbreeding pairs. Among breeding pairs, food intake varied with stage of egg formation but was lowest during egg laying, when egg formation costs were predicted to be highest. Female feeding behaviour (number of feeding bouts, peck rate) did not vary significantly during the laying cycle. Clutch size, but not egg size, was negatively correlated with food intake; that is, daily food intake was lowest for pairs in which females laid the largest clutches. Breeding pairs had much lower locomotor activity levels (114 hops h-1) than nonbreeding pairs (214 hops h-1), and activity declined sharply from 177 hops h-1 during the prelaying period to 106 hops h-1 at the start of the yolk-formation period. Clutch size was negatively correlated with locomotor activity on the day of peak energy demand for laying; that is, daily locomotor activity level was lowest for pairs in which females laid the largest clutches. Therefore, females reduced activity but did not increase food intake during the laying cycle, despite the additional energy requirements of egg production. These data suggest that the prevailing view of small passerines as "classic" income breeders needs to be reevaluated.

Animals↗
PubMedDate not supplied

Organ mass dynamics in relation to yolk precursor production and egg formation in European starlings Sturnus vulgaris.

Egg production in passerines and other birds requires rapid synthesis of proteins and lipids. We hypothesized that these biosynthetic demands would necessitate hypertrophy of the liver, which produces the yolk precursors vitellogenin and very low-density lipoprotein (VLDL), and of the metabolic machinery that supports the liver's biosynthetic activity (e.g., heart, kidneys, lungs, and digestive organs). To test this hypothesis, free-living female European starlings (Sturnus vulgaris) were collected through two breeding seasons. Change in liver mass in relation to breeding stage differed between years, as did the relationship between liver mass and plasma vitellogenin levels. In the first year, dry lean glycogen-free liver mass showed little seasonal variation and was not correlated with vitellogenin levels among egg-laying females. In the second year, liver mass was 4%-44% greater during egg laying than at other stages of breeding and was positively related to vitellogenin levels. In both years, the mass of the liver was not related to plasma VLDL levels. Thus, we did not find consistent relationships between liver mass and its biosynthetic output. In contrast to our hypotheses, the masses of the heart and digestive organs were lower during egg laying than they were before breeding. Meeting the biosynthetic demands of egg production does not appear to require hypertrophy of the liver or supporting metabolic machinery.

Animals↗
PubMedDate not supplied

Experimental (tamoxifen-induced) manipulation of female reproduction in zebra finches (Taeniopygia guttata).

Experimental manipulation of reproductive phenotype is a potentially powerful approach for understanding the fitness relationships of traits such as egg size, egg composition, and egg number. In this study, I investigated the effect of the antiestrogen tamoxifen on multiple, estrogen-dependent reproductive traits in female zebra finches (Taeniopygia guttata). Short-term tamoxifen treatment of egg-laying females (two daily injections before laying) had no effect on the timing or the pattern of egg laying compared to sham controls. However, tamoxifen treatment caused (1) a marked, but transient, decrease in egg size; (2) increased within-clutch egg-size variation; (3) a reduction in plasma vitellogenin (VTG) levels; and (4) lower dry yolk and yolk protein content of tamoxifen-treated females. Plasma levels of the second yolk precursor, very low density lipoprotein (VLDL), were not affected by tamoxifen, and tamoxifen appeared to have no effect on oviduct function in egg-laying females. These results are consistent with tamoxifen blocking estrogen receptors in the liver, suppressing VTG production, and decreasing the plasma pool of yolk precursors below a level required to maintain yolk formation at the normal rate. Tamoxifen treatment can therefore be used successfully to manipulate several components of the female reproductive phenotype (egg composition, intraclutch egg-size variation) to further explore the fitness consequences of these traits.

Animals↗
PubMedDate not supplied

Follicular development and plasma yolk precursor dynamics through the laying cycle in the European starling (Sturnus vulgaris).

We investigated the quantitative matching of plasma yolk precursor supply (the plasma pool) to follicle demand during yolk formation in European starlings (Sturnus vulgaris). Plasma concentrations of the two yolk precursors, vitellogenin (VTG) and very low density lipoprotein (VLDL), were only elevated coincident with rapid yolk development (RYD) and matched variation in total yolky follicle mass. VTG and VLDL were low (<0.4 microg/mL and <4.2 mg/mL, respectively) in nonbreeders and prebreeders with no yolky follicles, and at clutch completion. They increased to 4.02 microg/mL and 19.4 mg/mL in birds with a full follicle hierarchy (F1-F4), and concentrations then remained high and actually increased up to the point where only a single, yolky (F1) follicle remained. However, there was some evidence for mismatching of supply and demand: (a) precursor concentrations increased throughout the laying cycle even though the number of developing follicles decreased. We suggest that this is because of a requirement to maintain a large precursor pool to maintain high uptake rates; and (b) in birds with a full follicle hierarchy, precursor concentrations were negatively correlated with total follicle mass. This suggests that high uptake rates in large follicles can actually deplete circulating precursor concentrations. Plasma concentrations of both yolk precursors increased rapidly in the early morning with (predicted) time after ovulation, consistent with a lack of fine control of precursor concentrations. However, mean plasma VTG concentrations did not differ between morning or evening samples. In contrast, plasma VLDL concentrations were lower in the morning (16.8 mg/mL) than in the evening (22.9 mg/mL). Although there is marked individual variation in plasma VTG and VLDL (four- to eightfold), both precursors were repeatable in the short term (24 h), and plasma VTG was repeatable over a 14-d interval between successive breeding attempts.

Animals↗