PubMed Health⌕ Search

Biomedical subjects

G White

Publications and source records attributed to G White.

At least 19 recordsLinked to original sources
PubMed1995

An audit of the accuracy of upper gastrointestinal diagnoses in Scottish Morbidity Record 1 data in Tayside.

INTRODUCTION: Scottish Morbidity Record (SMR1) data are coded by trained clerical staff from case records and discharge summaries. They form the basis of many strategic NHS decisions. Their accuracy for upper gastrointestinal (UGI) diagnosis is unknown and the study was undertaken to assess this accuracy in Tayside. METHOD: Patients who fulfilled the following criteria were identified using a record-linkage pharmacoepidemiological database, and their case records retrieved: over 50 years of age, had encashed at least one prescription for a non-steroidal anti-inflammatory drug at a Tayside pharmacy and who had SMR1 records containing one or more symptom/diagnosis codes between January 1989 and December 1991. Medically qualified staff were trained to examine case records and to code UGI diagnoses. They searched the case records for every UGI SMR1 entry for these patients from 1980-1992 and produced re-coded diagnoses (RCD) for each hospital event (admission and discharge), using all the data available in the case records. They also abstracted data on the clinical presentation, investigations and management of patients. Each event was then examined by a single medically qualified researcher who compared the original SMR1 codes with the RCDs. RESULTS: 2,101 patients had a total of 3,764 events in 1989-1991. 317 events were either day case procedures or elective surgery or the case records were not found. They were therefore excluded. Of the remainder, the SMR1 and RCD codes were judged equivalent in 1,608 events (46.6%). However, 1,005 SMR1 events (29.2%) contained a symptom code but no diagnosis code and the remaining 834 (24.2%) were judged suboptimal for other reasons. Of those with a symptom code only, 406 could not be improved upon and were transformed into RCD symptom codes only, 435 were assigned symptom and diagnostic RCDs and 164 were assigned diagnostic RCDs only. In the other 834 events, 279 had one or more diagnoses missing, 425 had one or more diagnoses inaccurate, 23 had both missing and inaccurate diagnoses and 107 were not UGI. Thus 1,433 (41.6%) of UGI SMR1 events could be more accurately coded. Examination of investigation data revealed that coding inaccuracy was not due to diagnostic procedures being carried out after admission. CONCLUSION: UGI SMR1 data were satisfactory in about half of all events. In about a quarter there were symptom codes but no satisfactory diagnosis codes, whilst in another quarter the data were inaccurate. These findings have implications for health care activities and research that use these data.

Aged↗
PubMed1993

Ethanol action on excitatory amino acid activated ion channels.

The effects of ethanol on excitatory amino acid activated ion channels were investigated using patch-clamp recording methods. Intoxicating concentrations of ethanol (5-50 mM) inhibited ion current activated by the glutamate receptor agonist N-methyl-D-aspartate (NMDA) in a concentration-dependent manner (IC50 = 30 mM). The intoxicating potency of different alcohols was correlated with their potency for inhibiting NMDA-activated current, suggesting that alcohol-induced inhibition of NMDA channel function may contribute to the neural and cognitive impairments associated with intoxication. Analysis of mechanism suggests that ethanol inhibits NMDA-activated current by altering gating of the channel, rather than by affecting channel conductance, ion permeance or regulatory sites on the channel. Anesthetic concentrations of ethanol (> 50 mM) produced a concentration-dependent inhibition of kainate- and quisqualate-activated currents (IC50 = 220 mM), suggesting that this inhibition may contribute to the general anesthetic effects of ethanol. This hypothesis is supported by the observations that the general anesthetic agents, trichloroethanol (the active metabolite of chloral hydrate), pentobarbital and halothane, all inhibit kainate- and quisqualate-activated currents.

Animals↗
PubMed1992

Breast cancer survival among women under age 50: is mammography detrimental?

Great uncertainty exists about the benefit of detecting breast cancer by mammography in women under 50 years of age. We have reviewed the survival of patients aged 49 years or less whose cancers were detected by mammography alone. 117 women under the age of 50 years were diagnosed with breast cancer between 1978 and 1991 based only on an abnormal mammogram. Ductal carcinoma in-situ (DCIS) was found in 47 (40%) of these women, whilst 70 (60%) had infiltrating ductal or infiltrating lobular carcinomas. During the same interval, 928 women in this age group presented with palpable breast cancer. DCIS was diagnosed in 82 (9%) of these women, whilst 846 (91%) had infiltrating carcinoma. Among the infiltrating cancers detected by mammography alone, 50% were stage I, whilst only 30% of the women with palpable cancers were stage I. Five-year survival for all mammographically detected cancer patients was 95%, whereas for women with palpable cancers the survival was 74% (p < 0.00005). If DCIS is not included, the corresponding survivals are 91% for mammographically detected infiltrating cancers and 72% for palpable infiltrating cancers. Only 1 woman who died among those with palpable cancer had had a mammogram before diagnosis. Our data contradict the suggestion that women under 50 are put at a survival disadvantage by undergoing mammography. We believe that investigators who have reported negative results in this age group must examine other causes for their results.

Actuarial Analysis↗
PubMed1992

Pharmacokinetic properties of recombinant factor VIII compared with a monoclonally purified concentrate (Hemofil M). The Recombinate Study Group.

A recombinant FVIII preparation, Recombinate, was compared with a high-purity plasma-derived concentrate, Hemofil M, in 47 hemophilia A patients in a cross-over evaluation of pharmacokinetic properties. The recombinant material showed a significantly lower clearance, volume of distribution, and higher in vivo recovery, but a similar half-life to the plasma-based product. In a comparison with reported data from other standard concentrates, the recombinant preparation exhibited potentially better pharmacokinetic properties in that its clearance was slower and its half-life was longer. We conclude that the recombinant DNA method of preparation does not adversely affect the biological and pharmacological characteristics of the factor VIII molecule.

Adolescent↗
PubMed1992

1,9-Dideoxyforskolin does not mimic all cAMP and protein kinase A independent effects of forskolin on GABA activated ion currents in adult rat sensory neurons.

The effect of forskolin on GABAA receptor activated events has been the subject of recent investigations, the conclusions of which are conflicting. Forskolin can reduce current amplitude and increase the rate of decay of current activated by 100 microM GABA and these effects are not mimicked by 1,9-dideoxyforskolin (Tehrani et al., Synapse, 4 (1989) 126-131). On the other hand, both forskolin and 1,9-dideoxyforskolin inhibit 36Cl- flux induced by lower concentrations of muscimol (Heuschneider and Schwartz, Proc. Natl. Acad. Sci. USA, 86 (1989) 2938-2942). Using the whole-cell patch clamp technique to measure GABA activated current in dorsal root ganglion neurons that were freshly isolated from adult rats, we have confirmed the finding of Tehrani et al. (Synapse, 4 (1989) 126-131) using 100 microM GABA; however, the effects of forskolin that were not mimicked by 1,9-dideoxyforskolin were not blocked by the kinase inhibitor H-7 (50 microM). In contrast, at lower concentrations of GABA (10-20 microM), both forskolin and 1,9-dideoxyforskolin increased the decay rate of GABA activated current. In addition, all effects of forskolin occurred within 200 ms of application of forskolin and the effects were not blocked or occluded by H-7, 10 microM cAMP, or the active subunit of protein kinase A. We conclude that: (1) 1,9-dideoxyforskolin is not a reliable indicator of forskolin specificity in this system because its effects are dependent upon GABA concentration; and (2) the most prominent effects of forskolin on amplitude and decay time course of GABA activated ion current are not mediated by cAMP or protein kinase A (PKA).

Animals↗
PubMed1992

Heterogeneity in EC50 and nH of GABAA receptors on dorsal root ganglion neurons freshly isolated from adult rats.

GABA activates a Cl- current through the GABAA receptor/ionophore complex that influences excitability of neurons. Studies using expression of cloned cDNAs coding for different GABAA receptor/ionophore subunits suggest that the EC50 and Hill coefficient for GABA are influenced by subunit composition. However, no direct evidence for such heterogeneity has been reported for vertebrate neurons. I have investigated the heterogeneity of EC50 and Hill coefficients (nH) of isolated dorsal root ganglion neurons using the whole-cell patch clamp technique. The EC50 for GABA varied from 26 to 107 microM among neurons. nH calculated from the logistic equation varied from 1.18 to 2.0. A negative correlation was found between the EC50 and nH (r = -0.81). Both nH and EC50 differed between some cells. However, in some instances, nH differed between cells while EC50 values were similar, and in other cells, EC50 values differed and nH was similar. In addition, when cells were categorized according to action potential shape, the EC50 and Hill coefficients differed among cell types in some instances and were similar in other instances. These findings demonstrate that different pharmacological profiles for GABA can be observed in adult mammalian neurons. Selective distribution of such pharmacological subtypes of GABAA receptors may contribute to control of neuronal excitability.

Animals↗
PubMed1992

Effects of nerve growth factor on TTX- and capsaicin-sensitivity in adult rat sensory neurons.

We have investigated the effects of nerve growth factor (NGF, 2.5 ng/ml for 1-2 weeks) on enriched adult rat dorsal root ganglion (DRG) neurons maintained in cell culture in defined media. Whole-cell recordings in cells cultured in the absence and presence of NGF revealed no significant difference in resting membrane potential and input resistance. However, the threshold for spike generation was significantly lower in untreated cells than in treated cells; -25 +/- 1.1 mV vs -19 +/- 2.2 mV, respectively. The sensitivity of the Na+ spike to tetrodotoxin (TTX, 1 microM) was different in cells cultured in the absence or presence of NGF. For example, spikes were abolished by TTX in 100% of untreated cells, while in NGF-treated cells the spike was abolished in only 41% of the neurons. Chemosensitivity of DRG neurons was also different in the absence and presence of NGF. For example, the percent of neurons in which a current activated by 8-methyl-N-vanillyl-6-nonenamide (capsaicin, 500 nM) was detected, increased from 18% in untreated cells to 55% in NGF-treated cells. NGF did not influence the number of cells surviving. The results indicate that NGF can regulate TTX and capsaicin sensitivity in these adult rat sensory neurons. Our experimental protocol indicates that this effect is not mediated by a factor in the serum or released from non-neuronal cells.

Action Potentials↗
PubMed1992

pp39mos is associated with p34cdc2 kinase in c-mosxe-transformed NIH 3T3 cells.

We investigated the possible interactions between pp39mos and p34cdc2 kinase in NIH 3T3 cells transformed by c-mosxe. pp39mos is coprecipitated with p34cdc2 when using either anti-PSTAIR antibody or p13suc1-Sepharose beads. Likewise, p34cdc2 is coprecipitated with pp39mos when using anti-mos antibody. However, pp39mos was not present in histone H1 kinase-active p34cdc2 complexes precipitated with anti-p34cdc2 C-terminal peptide antibody even during metaphase of the cell cycle. The molar ratio of p34 to pp39mos in the p13suc1 complex is approximately 2:1. Consistent with the tight association between pp39mos and tubulin, tubulin was also present in equivalent amounts with pp39mos and p34 in the p13suc1 complex. This pp39mos-p34cdc2-tubulin complex may be important in transformation by the mos oncogene.

3T3 Cells↗
PubMed1992

Calcified suture material in the breast after radiation therapy.

Of 335 women who underwent lumpectomy and radiation therapy for breast cancer, 42 subsequently developed calcifications. Particles typical of calcified suture material were identified in 21 of the 42 women (50%). No obvious calcified suture material was found in approximately 1,140 women of 38,000 (3%) who had undergone mammography after they had previously undergone breast biopsy for a benign lesion and thus had not undergone radiation therapy. Calcified suture material rarely develops in the nonirradiated breast, but it is common after radiation therapy and should not be confused with recurrent breast cancer. These calcifications are likely the result of delayed resorption of catgut sutures, which provide a matrix on which calcium can precipitate in a suitable local environment.

Breast Neoplasms↗
PubMed1992

The source of pulsatile secretion of progesterone during the human follicular phase.

This study was designed to establish the normal pattern of serum progesterone and the origin of its secretion during the follicular phase of the normal menstrual cycle. In the first study, 12 normal women were studied on 3 occasions each at different times during a single follicular phase. Serum samples were collected every 10 min over 8 h, for 6 h before and 2 h after an injection of naloxone (5 mg iv). The mean serum progesterone remained constant (0.9 nmol/L) across the follicular phase until just before ovulation; individual subjects showed pulsatility of progesterone (1-6 pulses/6 h) but there was no relationship of this to LH pulsatility and no variation of progesterone pulsatility across the follicular phase. Naloxone caused an increase in the mean serum progesterone in the early follicular phase to 1.9 +/- 0.7 nmol/L and in the mid and late follicular phase to 2.1 +/- 0.7 nmol/L and 3.4 +/- 2.5 nmol/L, respectively. The second study was performed to assess the contribution of the residual corpus luteum and the developing follicle to the pulsatile secretion of progesterone. Seven anovulatory women with low levels of serum LH and absent LH pulsatility were studied before and after clomiphene (100 mg/day for 5 days) by collecting blood samples every 15 min for 6 h before GnRH (10 mg iv) and for 2 h afterwards. The anovulatory women had comparable mean serum concentration of progesterone (0.9 +/- 0.5 nmol/L) to normal women and similar frequency of progesterone pulsatility (2.1 +/- 1.1 pulses/6 h). After administration of clomiphene, there was no significant change in progesterone pulsatility (1.7 +/- 1.0 pulses/6 h) despite a substantial increase in LH pulsatility (from none to 3.0 +/- 1.0 pulses/6 h). There was no significant increase in serum progesterone after clomiphene or GnRH which both caused a substantial increase in serum LH. The third study involved eight normal women studied before and after treatment with dexamethasone (2 mg/day for 2 days) to assess the adrenal component of progesterone secretion. Blood samples were collected every 10 min for 6 h before and 2 h after naloxone (5 mg iv). Dexamethasone reduced serum progesterone to below assay sensitivity (less than 0.2 nmol/L) and obliterated progesterone pulsatility. The increase in serum progesterone and cortisol induced by naloxone was blocked by dexamethasone; the naloxone-induced rise of serum LH was not affected by dexamethasone. We conclude that neither the preceding corpus luteum nor the developing follicle are important contributors to the serum concentration of progesterone during the normal follicular phase.(ABSTRACT TRUNCATED AT 400 WORDS)

Activity Cycles↗
PubMed1992

GABA- and glutamate-gated ion channels as molecular sites of alcohol and anesthetic action.

The evidence presented above indicates that GABA- and glutamate-activated ion channels are molecular sites of alcohol and anesthetic action. In view of the important role that these channels play in CNS excitability, it seems likely that the actions of alcohol and anesthetics on these channels contribute significantly to the behavioral effects of these agents. Although the behavioral effects of alcohol and anesthetics may well result from a combination of actions on different ion channels and other molecular sites in the CNS, it is of interest to consider whether the actions of these agents on particular types of ion channels may contribute to particular behavioral effects. In this regard, it should be noted that benzodiazepines potentiate GABAA responses, but do not produce intoxication or general anesthesia in their clinical dose range. Benzodiazepines are widely used clinically, primarily for their anxiolytic actions (26), suggesting that the potentiation of GABAA responses by ethanol and barbiturates may contribute to the anxiolytic effects of these agents. Since kainate and quisqualate channels mediate fast excitatory transmission in the CNS, inhibition of kainate and quisqualate receptor-activated responses would be expected to result in general CNS depression. This suggests that inhibition of kainate and quisqualate receptor-mediated responses may contribute to the general anesthetic effects of ethanol, trichloroethanol and barbiturates. NMDA channels are thought to mediate complex excitatory neural phenomena and cognitive function. In view of this, the observation that ethanol inhibits NMDA receptor-mediated responses over the concentration range that produces intoxication and the correlation between the potency of different alcohols for inhibiting NMDA-activated current and their potency for producing intoxication suggest that ethanol-induced inhibition of NMDA receptor-mediated responses may contribute to the intoxicating effects of ethanol. Although these speculations are no doubt oversimplifications, the recognition that GABA- and glutamate-gated ion channels are molecular sites of alcohol and anesthetic action provides a basis for investigating the molecular mechanisms involved in the action of these agents and the behavioral significance of those actions.

Alcohols↗
PubMed1991

Construction, expression and characterization of humanized antibodies directed against the human alpha/beta T cell receptor.

Completely humanized antibodies with specificity for the human alpha/beta TCR have been produced by genetic engineering. The L and H chain V region exons encoding the murine mAb BMA 031 CD regions and human EU framework regions were synthesized and replaced into previously isolated genomic fragments. These fragments were inserted into mammalian expression vectors containing the human kappa and gamma 1 C region exons. Two variants were constructed each containing selected BMA 031 amino acids within the human frameworks. The humanized genes were transfected into Sp2/0 hybridoma cells by electroporation and transfectomas secreting humanized antibody were isolated. Levels of antibody expression up to 7 pg/cell/24 h were obtained. The humanized antibody, BMA 031-EUCIV2, competed poorly with murine BMA 031 for binding to T cells. BMA 031-EUCIV3, however, bound specifically to T cells and competed effectively with both the murine BMA 031 antibody and a previously constructed chimeric BMA 031 antibody for binding to these cells. The relative affinity of BMA 031-EUCIV3 was about 2.5 times lower than BMA 031. The ability to promote antibody dependent cell-mediated cytolysis was significantly enhanced with the engineered antibodies as compared to murine BMA 031. Humanized BMA 031 is a clinically relevant, genetically engineered antibody with potential uses in transplantation, graft vs host disease, and autoimmunity.

Amino Acid Sequence↗
PubMed1991

TTX-sensitive action potentials and excitability of adult rat sensory neurons cultured in serum- and exogenous nerve growth factor-free medium.

The excitability of adult rat dorsal root ganglion (DRG) neurons cultured in the absence of serum and exogenously added nerve growth factor (NGF) was studied. Current-clamp recordings revealed the presence of tetrodotoxin (TTX)-sensitive action potentials. Voltage-clamp recordings demonstrated the presence of both inward and outward currents. The inward Na+ current had a maximal amplitude near -10 mV and was completely blocked by TTX. A sustained Ca2+ inward current and a slowly activating outward K+ current were also observed. TTX-sensitive and TTX-resistant action potentials have been observed in previous studies in DRG neurons cultured in the presence of serum. By contrast, in the study reported here, only TTX-sensitive action potentials and Na+ currents were found in the neurons cultured in the absence of serum and nerve growth factor.

Action Potentials↗
PubMed1991

Sigma receptor ligands alter concentrations of corticosterone in plasma in the rat.

Both BMY-14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol hydrochloride) and gevotroline (WY-47384; 8-fluoro-2,3,4,5-tetrahydro-2-[3-(3-pyridinyl)-propyl]-1H-pyrido[4,3-b] indole hydrochloride) are known to antagonize the psychotomimetic action of N-allyl-normetazocine (NAN; SKF-10047) and exhibit a high affinity for the sigma receptor. Unexpectedly, the putative antagonists BMY-14802 and gevotroline acted like the agonist NAN and increased activity in the hypothalamic-pituitary-adrenal axis to elevate levels of corticosterone in plasma. During the acrophase (peak) of the effects of the circadian rhythm on the hypothalamic-pituitary-adrenal axis, the ED50 was 6.5 mmol/kg for BMY-14802 and 9.6 mmol/kg for gevotroline. The ED50s for BMY-14802 and gevotroline during the low activity phase were 15.8 and 21.2 mmol/kg, respectively. The efficacies during both phases of the circadian rhythm were similar for each drug. Additive effects on the levels of corticosterone in plasma were observed when the animals were pretreated with doses above the respective ED50 values and then subjected to a rotational stress, but a small dose of BMY-14802 (0.5 mg/kg) had the opposite effect and completely inhibited the stress-related increases in corticosterone in plasma. Neither drug, at large doses, altered the increase in levels of corticosterone in plasma generated by the circadian rhythm, but at smaller doses BMY-14802 did lower circadian-related levels of corticosterone. Pretreatment with dexamethasone blocked the gevotroline-related increase in corticosterone in plasma, but not the BMY-14802-related increase. These data suggest that central sigma receptor mechanisms are involved in the regulation of the hypothalamic-pituitary-adrenal axis and that therapeutic agents that affect these receptors may alter the activity in this axis.

Animals↗
PubMed1991

Differential staining of human alpha beta and gamma delta T cells by the fluorescein conjugate of an anti-CD3 monoclonal antibody.

The enumeration of total T cells, an important function of the clinical immunology laboratory, utilizes antibodies to CD3, the macromolecular complex associated with the antigen-specific receptors of T cells. We compared the ability of some commonly employed commercial anti-CD3 reagents to stain human peripheral blood lymphocytes. Surprisingly, the fluorescein isothiocyanate (FITC) conjugate of Coulter clone T3 (FITC-T3) stained most T cells brightly, but selectively stained gamma delta T cells very dimly or not at all. In contrast, the other anti-CD3 reagents studied (FITC-Leu 4, PE-T3, PE-Leu 4, and indirectly labelled T3 and Leu 4) stained all T cells equivalently. Dual-colour flow cytometric analysis with FITC-T3 and PE-Leu 4 readily demonstrated a FITC-T3-/PE-Leu 4+ population of T cells. This unique population stained dimly or not at all with a combination of anti-CD4 and anti-CD8 monoclonal antibodies and positively with the pan-gamma delta T cell antibody TCR delta 1. Moreover, an excellent correlation was found between the number of FITC-T3-/PE-Leu 4+ cells and the number of TCR delta 1+ cells in 32 normal individuals. Thus, the FITC-T3-/PE-Leu 4+ phenotype accurately marks all gamma delta T cells. In contrast to FITC-T3, both PE-conjugated and unconjugated T3 stained gamma delta T cells brightly. Therefore, T3 binds to an epitope present on all T cells, but fluoresceinylation specifically attenuates this antibody's ability to bind to gamma delta T cells. These findings indicate that the use of FITC-T3 can result in a significant and variable underestimation of peripheral blood T cell number and demonstrate further that the CD3 complexes of human alpha beta and gamma delta T cells are significantly different.

Adult↗
PubMed1991

Alcohol and anesthetic actions on excitatory amino acid-activated ion channels.

The actions of alcohol and anesthetics have been studied on excitatory amino acid activated ion channels in mammalian neurons. Ethanol inhibits NMDA-activated current over a concentration range that produces intoxication, and the potency of several alcohols for inhibiting the NMDA-activated current is correlated with their intoxicating potency, suggesting that alcohol-induced inhibition of responses to NMDA receptor activation may contribute to the neural and cognitive impairments associated with intoxication. Studies on the mechanism of ethanol inhibition of NMDA-activated current indicate that ethanol does not appear to block the ion channel, alter the ion selectivity of the channel, or interact with previously described binding sites on the NMDA receptor/ionophore complex. The linear relation between the potency of several alcohols for inhibiting the NMDA-activated current and the hydrophobicity of the alcohols suggests that ethanol may inhibit the NMDA-activated ion current by a novel type of interaction with a hydrophobic site associated with the NMDA channel. In addition, different types of general anesthetic agents exhibit different inhibitory actions on NMDA-, kainate-, and quisqualate-activated currents, suggesting that differences in the profile of inhibition of excitatory amino acid neurotransmission in the CNS among different classes of general anesthetics may contribute to the differences in their behavioral and physiological effects.

Alcohols↗