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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 541 records · Page 30Linked to original sources
PubMed1993

Isolation and characterization of a rat cDNA clone encoding a secreted superoxide dismutase reveals the epididymis to be a major site of its expression.

Superoxide dismutase (SOD) plays a key role in combating loss of fertility of spermatozoa due to lipid peroxidation. Here we report the sequence of a cDNA encoding a secreted form of SOD isolated from a rat epididymal library. Northern-blot analysis indicates that the corresponding transcript is expressed principally in the cauda region of the epididymis, consistent with the high levels of SOD enzyme activity found in cauda-epididymidal plasma. Much lower levels of an identically sized transcript exist in all tissues examined, including placenta. PCR and subsequent sequence analysis of rat placental SOD strongly suggest that it is identical in sequence with epididymal SOD.

Amino Acid Sequence↗
PubMed1993

Specificity of binding of zona pellucida glycoproteins to sperm proacrosin and related proteins.

A major regulatory site for species specificity of fertilization in mammals lies at the level of sperm binding to the zona pellucida. This implies a high degree of complementarity between gamete receptor molecules. One putative receptor molecule on spermatozoa is proacrosin/acrosin which binds to zona pellucida glycoproteins (ZPGPs) non-enzymically and with high affinity. The mechanism of recognition involves polysulphate groups in a particular stereochemical orientation and it has been suggested that this may contribute to species specificity of sperm-egg binding. In the present work this hypothesis has been tested by challenging 125I-labelled ZPGPs from pig, cow, and hamster eggs to recognize heterologous sperm proacrosins as well as a variety of sequence-related and unrelated proteins. Results show that pig and cow 125I-ZPGPs bind readily to boar, ram, and bull proacrosin but do not recognize guinea-pig proacrosin or any of the polysulphate binding proteins from rat, hamster, or mouse spermatozoa. Hamster 125I-ZPGPs also recognise boar, ram, and bull proacrosin as well as a range of unidentified proteins in pH3 extracts of hamster, rat, and mouse spermatozoa. The binding of ZPGPs to a variety of proteins not related to proacrosin is strongest to those with a high content of basic residues (i.e., pI > 8.5), although the secondary folding of the target protein is of major importance as boar proacrosin (pI 6.75) has the highest binding capacity of all proteins tested. Cross-reaction of ZPGP probes was not observed to guinea-pig proacrosin, suggesting that in this species the conformation of the protein is different to other sperm proacrosins.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosin↗
PubMed1993

Lead-contaminated soil abatement and urban children's blood lead levels.

OBJECTIVE: To test the hypothesis that a reduction of 1000 ppm or more of lead in soil accessible to children would result in a decrease of at least 0.14 mumol/L (3 micrograms/dL) in blood lead levels. SETTING: Urban neighborhoods with a high incidence of childhood lead poisoning and high soil lead levels. DESIGN: Randomized controlled trial of the effects of lead-contaminated soil abatement on blood lead levels of children followed up for approximately 1 year after the intervention. PATIENTS: A total of 152 children less than 4 years of age with venous blood lead levels of 0.34 to 1.16 mumol/L (7 to 24 micrograms/dL). Children were largely poor and had a mean age at baseline of 32 months, a mean blood lead level of 0.60 mumol/L (12.5 micrograms/dL), and a median surface soil lead level of 2075 ppm. INTERVENTIONS: Children were randomized to one of three groups: the study group, whose homes received soil and interior dust abatement and loose paint removal; comparison group A, whose homes received interior dust abatement and loose paint removal; and comparison group B, whose homes received only interior loose paint removal. MAIN OUTCOME MEASURES: Change in children's blood lead levels from preabatement levels to levels approximately 6 and 11 months after abatement. RESULTS: The mean decline in blood lead level between preabatement and 11 months after abatement was 0.12 mumol/L (2.44 micrograms/dL) in the study group (P = .001), 0.04 mumol/L (0.91 microgram/dL) in group A (P = .04), and 0.02 mumol/L (0.52 microgram/mL) in group B (P = .31). The mean blood lead level of the study group declined 0.07 mumol/L (1.53 micrograms/dL) more than that of group A (95% confidence interval [CI], -0.14 to -0.01 mumol/L [-2.87 to -0.19 micrograms/dL]) and 0.09 mumol/L (1.92 micrograms/dL) more than group B (95% CI, -0.16 to -0.03 mumol/L [-3.28 to -0.56 micrograms/dL]). When adjusted for preabatement lead level, the 11-month mean blood lead level was 0.06 mumol/L (1.28 micrograms/dL) lower in the study group as compared with group A (P = .02) and 0.07 mumol/L (1.49 micrograms/dL) lower than in group B (P = .01). The magnitude of the decline independently associated with soil abatement ranged from 0.04 to 0.08 mumol/L (0.8 to 1.6 micrograms/dL) when the impact of potential confounders, such as water, dust, and paint lead levels, children's mouthing behaviors, and other characteristics, was controlled for. CONCLUSIONS: These results demonstrate that lead-contaminated soil contributes to the lead burden of urban children and that abatement of lead-contaminated soil around homes results in a modest decline in blood lead levels. The magnitude of reduction in blood lead level observed, however, suggests that lead-contaminated soil abatement is not likely to be a useful clinical intervention for the majority of urban children in the United States with low-level lead exposure.

Child, Preschool↗
PubMed1993

On the application of the minimal principle to solve unknown structures.

The Shake-and-Bake method of structure determination is a new direct methods phasing algorithm based on a minimum-variance, phase invariant residual, which is referred to as the minimal principle. Previously, the algorithm had been applied only to known structures. This algorithm has now been applied to two previously unknown structures that contain 105 and 110 non-hydrogen atoms, respectively. This report focuses on (i) algorithmic and parametric optimizations of Shake-and-Bake and (ii) the determination of two previously unknown structures. Traditional tangent formula phasing techniques were unable to unravel these two new structures.

Algorithms↗
PubMed1993

Sequence analysis of monkey acrosin-trypsin inhibitor transcripts and their abundant expression in the epididymis.

Seven independent cross-hybridizing clones have been isolated from a Macaca fascicularis epididymal cDNA library and their inserts shown to correspond to a secreted inhibitor of the sperm serine proteinase, acrosin. Hybridizing transcripts of approx. 0.6 kb have been shown by Northern blot analysis to be considerably more abundant in the epididymis than the testis. This finding is in surprising contrast to a previous report that human acrosin-trypsin inhibitor mRNA predominates in the testis.

Amino Acid Sequence↗
PubMed1993

Psychotherapy and bulimia nervosa. Longer-term effects of interpersonal psychotherapy, behavior therapy, and cognitive behavior therapy.

OBJECTIVE: To determine whether cognitive behavior therapy (CBT) for bulimia nervosa has a specific therapeutic effect and determine whether a simplified behavioral treatment (BT) of CBT is as effective as the full treatment. DESIGN: Randomized controlled trial involving three psychological treatments. Two planned comparisons, CBT with interpersonal psychotherapy (IPT), and CBT with BT. Closed 12-month follow-up period. Independent assessors. SETTING: Secondary referral center. PATIENTS: Seventy-five consecutively referred patients with bulimia nervosa. Patients with concurrent anorexia nervosa were excluded. INTERVENTIONS: Cognitive behavior therapy, IPT, BT conducted on an individual outpatient basis. There were nineteen sessions over 18 weeks. Six experienced therapists administered all three treatments. There was no concurrent treatment. MAIN OUTCOME MEASURE: Frequency of binge eating and purging. RESULTS: High rate (48%) of attrition and withdrawal among the patients who received BT. Over follow-up, few patients undergoing BT met criteria for a good outcome (cessation of all forms of binge eating and purging). Patients in the CBT and IPT treatments made equivalent, substantial, and lasting changes across all areas of symptoms, although there were clear temporal differences in the pattern of response, with IPT taking longer to achieve its effects. CONCLUSIONS: Bulimia nervosa may be treated successfully without focusing directly on the patient's eating habits and attitudes to shape and weight. Cognitive behavior therapy and IPT achieved equivalent effects through the operation of apparently different mediating mechanisms. A further comparison of CBT and IPT is warranted. The behavioral version of CBT was markedly less effective than the full treatment.

Adolescent↗
PubMed1993

Postoperative chemotherapy without radiation in young children with malignant non-astrocytic brain tumours. A report from the Australia and New Zealand Childhood Cancer Study Group (ANZCCSG).

Young children with malignant brain tumours have particularly poor survival and manifest severe sequelae of radiation therapy. A multi-institutional pilot study of post-operative primary chemotherapy for children under 3 years with primitive neuroectodermal tumours (PNET) or ependymoma was initiated in 1987. The chemotherapy protocol comprised carboplatin, vincristine and the "eight drugs in 1 day" regimen. Radiation was recommended only if tumour progression or recurrence was documented. A total of 14 patients between 5 and 36 months of age were enrolled. Seven had supratentorial tumours (PNET, pinealoblastoma, intracranial retinoblastoma) with multiple predictors of adverse outcome. Four of these responded to initial chemotherapy but subsequently progressed and all had died by 16 months from diagnosis. The seven patients with infratentorial tumours (three medulloblastomas, four ependymomas) had more favourable predictors of outcome: no meningeal dissemination and gross macroscopic resection in six of the seven cases. One patient progressed rapidly and died within 5 months. The other six are alive at 37-57 months from diagnosis. Four are in continuous complete remission at 57, 51, 41 and 37 months, respectively from the time of their tumour resection. One is described as having stable disease with a persistent radiographic lesion at 41 months from diagnosis. One has relapsed on two occasions and is the only surviving patient to have been irradiated. Intelligence scores for the six long-term survivors have thus for remained within the normal range. It is suggested that some infants with standard-risk ependymoma and, possibly, medulloblastoma may be cured without radiation therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Changes during treatment for bulimia nervosa: a comparison of three psychological treatments.

Seventy-five patients with bulimia nervosa were treated with cognitive behaviour therapy, behaviour therapy or interpersonal psychotherapy. The changes that occurred during treatment were assessed in a subsample of 38 patients. There was an immediate decrease in the frequency of binge-eating and purging (self-induced vomiting or laxative misuse). This continued for 4 wk in interpersonal psychotherapy and for 8 wk in the other two treatment conditions. There were no clear differences between the three treatments in the time course of their effects on a global measure of eating behaviour and attitudes or on measures of depression and self-esteem. The findings suggest that certain shared 'non-specific' properties of psychological treatments can have a substantial early effect on the eating behaviour of patients with bulimia nervosa. Indeed, patients with bulimia nervosa may be particularly likely to show non-specific treatment effects. Cognitive behaviour therapy and behaviour therapy appear to have an immediate influence on eating behaviour over and above these non-specific effects. The study gave no clues as to the mechanism of action of interpersonal psychotherapy.

Adult↗
PubMed1993

Positron emission tomographic studies of [11C]MDL 72222, a potential 5-HT3 receptor radioligand: distribution, kinetics and binding in the brain of the baboon.

The drug MDL 72222, a selective 5-HT3 receptor antagonist, was labelled with 11C and evaluated for distribution kinetics in brain and in vivo binding to 5-HT3 receptors using cold MDL 72222 challenge and positron emission tomography (PET), in three anaesthetized baboons. After tracer doses of [11C]MDL 72222 (i.v. bolus), 11C radioactivity was equally partitioned between plasma and blood cells and readily crossed the blood-brain barrier; it was distributed heterogeneously into 17 different structures of the brain. The kinetic curves for 11C in tissue showed a rapid initial uptake, followed by a slower ascending phase, up to about the twentieth minute and by a plateau, until the end of experiment (90 min). The plateau values indicated marked uptake in brain which, however, varied according to the region considered. In inhibition studies with cold MDL 72222 (1 mg.kg-1) as pretreatment, co-injection or displacement, no clear-cut effects on the kinetics of [11C] MDL 72222 in brain were detected in any region, including those known to be rich in 5-HT3 receptors. These observations suggest that specific binding to 5-HT3 receptors was not detectable in brain in vivo, because of the high lipophilicity (thus a great capacity for non-specific binding) of MDL 72222. These negative findings may also result from both the possible suboptimal affinity of MDL 72222 for 5-HT3 receptors in vivo and the relatively low density of 5-HT3 receptors present only in selected areas of the mammalian brain. This study is a step in the search of selective 5-HT3 receptor radioligands, adequate for in vivo applications. Slow clearance of [11C]MDL 72222 from brain tissue in baboons, should be accounted for in clinical pharmacokinetic investigations for optimal posology considerations.

Animals↗
PubMed1993

Use of remote video microscopy (telepathology) as an adjunct to neurosurgical frozen section consultation.

We investigated the use of remote video microscopy (telepathology) to assist in the diagnosis of 52 neurosurgical frozen section cases. The TelMed system (Discovery Medical Systems, Overland Park, KS), in which the referring pathologist selects appropriate fields for transmission to the consultant, was used for the study. There was a high degree of concordance between the diagnosis rendered on the basis of transmitted video images and that rendered on the basis of direct evaluation of frozen sections; however, in seven cases there was substantial disagreement. Remote evaluation was associated with a more rapid consultation from the standpoint of the consultant, who spent approximately 2 minutes less per case when using remote microscopy; this was achieved at the expense of considerably greater effort on the part of the referring pathologist, who spent approximately 16 minutes per case selecting an average of 4.5 images for transmission to the consultant. The use of remote video microscopy for pathology consultation is associated with a complex series of tradeoffs involving cost, information loss, and timeliness of consultation.

Frozen Sections↗
PubMed1993

Predictors of 12-month outcome in bulimia nervosa and the influence of attitudes to shape and weight.

Seventy-five patients with bulimia nervosa were treated with 1 of 3 short-term psychological treatments and were then entered into a closed 1-year period of follow-up. Pretreatment predictors of 3 measures of outcome were sought. Only 2 variables were significantly associated with outcome: attitudes toward shape and weight, and self-esteem. The nature of the relation between attitudinal disturbance and outcome was complex and unexpected. The data set was also used to test the major prediction of the cognitive view of bulimia nervosa, namely that among patients who have responded to treatment, the residual level of attitudinal disturbance will predict subsequent outcome. This prediction was confirmed.

Attitude↗
PubMed1993

Effects of local anesthetics on single channel behavior of skeletal muscle calcium release channel.

The effects of the two local anesthetics tetracaine and procaine and a quaternary amine derivative of lidocaine, QX314, on sarcoplasmic reticulum (SR) Ca2+ release have been examined by incorporating the purified rabbit skeletal muscle Ca2+ release channel complex into planar lipid bilayers. Recordings of potassium ion currents through single channels showed that Ca(2+)- and ATP-gated channel activity was reduced by the addition of the tertiary amines tetracaine and procaine to the cis (cytoplasmic side of SR membrane) or trans (SR lumenal) side of the bilayer. Channel open probability was lowered twofold at tetracaine and procaine concentrations of approximately 150 microM and 4 mM, respectively. Hill coefficients of 2.0 and greater indicated that the two drugs inhibited channel activity by binding to two or more cooperatively interacting sites. Unitary conductance of the K(+)-conducting channel was not changed by 1 mM tetracaine in the cis and trans chambers. In contrast, cis millimolar concentrations of the quaternary amine QX314 induced a fast blocking effect at positive holding potentials without an apparent change in channel open probability. A voltage-dependent block was observed at high concentrations (millimolar) of tetracaine, procaine, and QX314 in the presence of 2 microM ryanodine which induced the formation of a long open subconductance. Vesicle-45Ca2+ ion flux measurements also indicated an inhibition of the SR Ca2+ release channel by tetracaine and procaine. These results indicate that local anesthetics bind to two or more cooperatively interacting high-affinity regulatory sites of the Ca2+ release channel in or close to the SR membrane. Voltage-dependent blockade of the channel by QX314 in the absence of ryanodine, and by QX314, procaine and tetracaine in the presence of ryanodine, indicated one low-affinity site within the conduction pathway of the channel. Our results further suggest that tetracaine and procaine may primarily inhibit excitation-contraction coupling in skeletal muscle by binding to the high-affinity, regulatory sites of the SR Ca2+ release channel.

Anesthetics, Local↗