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G Allen

Publications and source records attributed to G Allen.

At least 19 recordsLinked to original sources
PubMed1992

Analysis of exon 7 of the human phenylalanine hydroxylase gene: a mutation hot spot?

Complete sequence analysis of 194 human phenylalanine hydroxylase genes from PKU patients originating from West Germany and Bulgaria revealed 13 different mutations within exon 7 of the gene. Four of these mutations (T238P: ACT-->CCT; L242F:CTC-->TTC; R252G:CGG-->GGG; and 1043 delta 11: nt 1043-nt 1053 deleted) have so far not been described in the literature. Including these new mutations at least 21 different gene lesions and one sequence polymorphism exist for exon 7. Despite this large number unbiased calculation of the mutation frequency/exon size ratio does not provide conclusive evidence that exon 7 is a hot spot for disease causing mutations. Extensive screening during our experiments also failed to demonstrate the existence of excessive polymorphism in this part of the gene. It might therefore be speculated that the functional importance of the highly conserved exon 7 sequence accounts for the clustering of observed mutations which result in clinically manifest PKU. In addition we report our experience in regard to the resolution capacity of denaturing gradient gel electrophoresis (DGGE), a nonradioactive technique for the rapid screening of unknown mutations in exon 7.

Alleles↗
PubMed1992

Twinning and the r/K reproductive strategy: a critique of Rushton's theory.

The theory of r selection, favoring population growth, as opposed to K selection, favoring more efficient utilization of resources, has in recent years been applied by Rushton to contrast human ethnic groups in terms of their r/K reproductive strategies, suggesting the existence of a continuum from r groups, producing many offspring but providing little parental care, to K groups, producing few offspring but providing much parental care. Rushton's theory, which is largely based on ethnic differences in twinning rates, is here critically examined. It is pointed out that twinning rate differences are not necessarily genetic in origin since various environmental factors clearly play a role, and also that twinning, as a mode of reproduction, is not necessarily an r strategy, considering the high prenatal and perinatal selection to which it has been, and still is, associated. Moreover, Rushton misinterprets a number of relevant aspects related to the biology of twinning. The claim that ethnic differences in twinning rates provide evidence for an r/K typology in human populations with respect to reproductive strategies does not appear to be warranted.

Animals↗
PubMed1992

Digoxin and digoxin derivative induced arrhythmias: in vitro binding and in vivo abolition of arrhythmias by digoxin immune Fab (DIGIBAND).

OBJECTIVE: The aim was to compare the binding characteristics of a highly purified digoxin specific antigen binding fragment (digoxin immune Fab: DIGIBIND) with digoxin and with two commonly used derivatives of digoxin, beta methyl digoxin and beta acetyl digoxin, and to assess its ability to abolish the arrhythmogenic effects of these digitalis glycosides. METHODS: The binding characteristics of DIGIBIND with digoxin, beta methyl digoxin, and beta acetyl digoxin were assessed in vitro by measuring their ability to inhibit the binding of DIGIBIND to 3H-digoxin. From these studies the affinities of the interactions between DIGIBIND and these glycosides, and the binding capacity of DIGIBIND for each of these glycosides, could be measured. The ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin, beta methyl digoxin, and beta acetyl digoxin was assessed using an in vivo anaesthetised guinea pig model (n = 36, weight 300-400 g), in which these glycosides were infused intravenously (50 micrograms.kg-1 x min-1) until the onset of ventricular arrhythmias, at which point the total amount of glycoside given was calculated. A single bolus dose of either vehicle or DIGIBIND was then given intravenously, and the time to restoration of normal cardiac rhythm noted. After the administration of DIGIBIND, a second infusion of the same glycoside was given to reinitiate the ventricular arrhythmias. The time to onset of the arrhythmias was noted, and the additional amount of glycoside given calculated. RESULTS: In vitro studies showed the binding of DIGIBIND to 3H-digoxin to be inhibited by digoxin and by the two derivatives. The affinities of these interactions with DIGIBIND were significantly different, that for digoxin being some twofold greater than that for beta methyl digoxin and beta acetyl digoxin. The ED50 concentrations were 14.1 (95% CI 12.2, 15.2), 29.2(26.1, 32.7), and 36.2(33.0, 39.8) nM, respectively. However, there were no significant differences between these glycosides in their binding capacities. The in vivo studies showed that intravenous infusion of digoxin, beta methyl digoxin, or beta acetyl digoxin induced similar ventricular arrhythmias. The onset of the arrhythmias was clearly discernible, and required a significantly lower dose of digoxin compared with that of beta methyl digoxin and beta acetyl digoxin. These doses were 667(SEM 55), 868(33), and 854(40) nmol.kg-1, respectively. Termination of the infusion had no effect on the arrhythmias, and in those animals which received a bolus intravenous injection of saline there was no return to normal cardiac rhythm. By contrast, in animals which received a bolus intravenous injection of DIGIBIND, there was complete abolition of the arrhythmias within 4-6 min. Although the dose of DIGIBIND given to abolish digoxin induced arrhythmias was approximately 25% less than that given to abolish beta methyl digoxin and beta acetyl digoxin induced arrhythmias (p < 0.05), the time to restoration of normal cardiac rhythm after DIGIBIND was not significantly different for digoxin compared with beta methyl digoxin and beta acetyl digoxin, at 4.6(0.9), 4.9(0.8), and 5.7(0.8) min, respectively. To reinitiate the arrhythmias in those animals which had received DIGIBIND, a dose of glycoside was required which was not significantly different from that given prior to the DIGIBIND. This observation therefore confirmed the stoichiometric relationship between DIGIBIND and each of the glycosides in respect of the neutralising action of DIGIBIND in abolishing the arrhythmogenic effects of these agents. CONCLUSIONS: Although there is some small difference in the affinities of the binding interactions, there is no difference in the binding capacities of DIGIBIND for digoxin, beta methyl digoxin, or beta acetyl digoxin in vitro. These binding interactions are manifest as the ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin and the two derivatives in vivo.

Acetyldigoxins↗
PubMed1992

A bronchogenic cyst causing respiratory distress.

A case is reported of acute respiratory distress in an adult that was caused by a bronchogenic cyst. Bronchogenic cyst in an adult may be seen on chest X-ray and confirmed by computerized tomography (CT) scanning. Surgical excision can provide dramatic relief.

Adult↗
PubMed1992

Experimental comparison of the effects of three treatment programs for homeless mentally ill people.

A longitudinal experimental design was used to compare the effectiveness of three community-based treatment programs serving homeless mentally ill people: traditional outpatient treatment offered by a mental health clinic, a daytime drop-in center, and a continuous treatment team program that included assertive outreach, a high staff-to-client ratio, and intensive case management. At 12-month follow-up, clients in all three treatment programs spent fewer days per month homeless, showed fewer psychiatric symptoms, and had increased income, interpersonal adjustment, and self-esteem. Clients in the continuous treatment program had more contact with their treatment program, were more satisfied with their program, spent fewer days homeless, and used more community services and resources than clients in the other two programs.

Activities of Daily Living↗
PubMed1991

Vacuum tumescence devices: the role of papaverine in the selection of patients.

We conducted a prospective study to determine the positive predictive value of papaverine testing to select patients in whom a vacuum constriction device would be a successful alternative to operative management of impotence. A total of 30 men presenting to an impotence clinic was evaluated with a series of papaverine dosages up to 60 mg. These patients then received a physician-administered trial of a vacuum constriction device, followed by 3 months of home use and a repeat objective evaluation. Initial responses to the device were poor, with 46% of the patients (14) achieving a rigid erection. However, after 3 months of home use 83% of the patients (25) achieved a rigid erection. The positive predictive value of a good response to the papaverine trial was 94%.

Equipment Design↗
PubMed1991

A blinded comparison of noninvasive, in vivo phosphorus nuclear magnetic resonance spectroscopy and the in vitro halothane/caffeine contracture test in the evaluation of malignant hyperthermia susceptibility.

Malignant hyperthermia (MH) is a potentially fatal, anesthetic-induced syndrome. Currently, the only accurate means of diagnosing susceptibility to this syndrome is the testing of biopsied skeletal muscle for its contracture response to halothane and caffeine. A less invasive means of diagnosis is needed. The authors previously reported that MH-susceptible patients studied by in vivo phosphorus nuclear magnetic resonance (31P NMR) spectroscopy demonstrated a higher resting inorganic phosphate (Pi) to phosphocreatine (PCr) ratio in their skeletal muscle, as well as a slower postexercise recovery of PCr/Pi, when compared to normal controls. In the present blinded study, the authors compared in vivo 31P NMR determination of resting Pi/PCr and recovery rate of PCr/Pi in forearm muscles to in vitro halothane/caffeine contracture test results in 42 patients. Forty-three control subjects were studied to establish normal NMR values of resting Pi/PCr and recovery rate of PCr/Pi. Their findings were compared with those of 27 patients shown to be MH-susceptible and 15 patients MH-negative by contracture testing. The MH-susceptible group had a significantly (P less than 0.005) higher resting Pi/PCr value (0.202 +/- 0.044) than either the MH-negative (0.152 +/- 0.043) or the control (0.141 +/- 0.026) group. The MH-susceptible group also had a significantly (P less than 0.02) slower postexercise recovery rate of PCr/Pi (1.50 +/- 0.872 PCr.Pi-1.min-1) than either the MH-negative (2.11 +/- 1.07 PCr.Pi-1.min-1) or control (2.25 +/- 0.828 PCr.Pi-1.min-1) group. Twenty-six of the 27 MH-susceptible patients demonstrated abnormal NMR test results (a resting Pi/PCr greater than or equal to 0.18 or recovery rate less than 1.0 PCr.Pi-1.min-1), and 13 of the 15 MH-negative patients had normal NMR results. Although neither NMR parameter alone was diagnostically reliable, an NMR test utilizing both parameters was quite accurate. The NMR test and contracture test demonstrated an overall agreement of 93% with a copositivity of 96% and conegativity of 87%. The sensitivity and specificity of the NMR test is estimated to be 98.8% +/- 11.8% and 95.3% +/- 20.3%, respectively. The role of 31P NMR in the diagnosis of MH susceptibility and possible mechanisms underlying the observations are discussed.

Adolescent↗
PubMed1979

Identification of the amino acid residues of proteins S5 and S8 adjacent to each other in the 30 S ribosomal subunit of Escherichia coli.

When Escherichia coli 30 S ribosomal subunits are reacted with protein-protein bifunctional reagents, a number of protein pairs as well as aggregates containing three or more ribosomal proteins are formed. In the present study we have purified one of the protein pairs obtained by reaction of 30 S ribosomal subunits with either radioactive or nonradioactive dimethylsuberimidate. Following molecular weight determination and ammonolysis, the pair was shown to consist of ribosomal proteins S5 and S8. The "native" structure of the complex was surmised from its capacity to be reconstituted into a biologically active 30 S ribosomal subunit. From peptide maps and primary structure determination of various peptides it was demonstrated that the cross-linking bond between ribosomal proteins S5 and S8 involves primarily the residues Lys-93 of protein S8 and the COOH-terminal lysine (Lys-166) of ribosomal protein S5. This result is substantiated by the finding that a mutant carrying an altered S5 lacking the COOH-terminal lysine yields a greatly reduced amount of S5-S8 cross-link. In addition to the points of cross-linking it was found that Lys-30, Lys-68, and Lys-86 of S8 and Lys-5 of S5 react with dimethylsuberimidate, indicating that these residues are available for reaction and suggesting their topographical localization on the ribosomal surface.

Amino Acid Sequence↗
PubMed1979

Holzinger's Hc revised.

The formula H'C = 1 - CDZ/CMZ is suggested as a better summary of twin concordance data than the familiar Holzinger concordance formula, HC = (CMZ - CDZ)/(1 - CDZ). The new formula better estimates degree of genetic determination, G, as calculated from a threshold model, but never exceeds unity, as G sometimes does. For high concordance rates, if CMZ + CDZ greater than 1, HC may be more useful than either G or H'C.

Female↗
PubMed1979

Twin concordance. A more general model.

Estimation of the twin concordance rate for a disease often requires two stages. First, the disease is ascertained in a population or in a population sample, and such twins as are found with the disease become probands. Second, twin pairs with only one proband are further investigated and additional concordant pairs are thus discovered. A mathematical model is presented that allows for continuous variation in completeness of ascertainment in both stages, for correlation within pairs in the primary ascertainment process, and for correlation within pairs in occurrence of the disease. The concordance rate can be estimated by the proband method if secondary ascertainment is complete; other measures of concordance are accurate only if primary ascertainment is complete. A parameter analogous to the concordance rate but related to correlation in primary ascertainment can be estimated from the same data.

Age Factors↗
PubMed1979

The effects of graded experimental trauma on cerebral blood flow and responsiveness to CO2.

The effects of graded mechanical cerebral trauma on cerebrovascular reactivity to CO2 was studied in 26 cats. A fluid-wave percussion model was employed which delivered an epidural trauma of fixed duration and variable amplitude. The animals were maintained at arterial normoxia, with constant monitoring of intracranial and systemic arterial pressures, electroencephalograms, and end-tidal CO2. Following trauma, cerebral blood flow was measured using the H2 ion clearance technique at PaCO2 levels ranging sequentially from 20 to 60 mm Hg. Cerebrovascular reactivity for control animals (uninjured) was 2.7%. In the group with mild trauma (0.76 to 1.90 atm) reactivity was impaired (1.7%), and it was abolished in the severely injured group (2.90 to 4.60 atm). Mild injuries did not alter resting blood flows, while severe trauma resulted in a significant decrease in cerebrovascular resistance. Intracranial and systemic arterial pressures were altered proportionately to the level of cerebral injury. The authors propose that trauma to the brain-stem vasoregulatory centers accounts for these findings.

Animals↗
PubMed1978

Primary structures of cysteine-containing peptides from the calcium ion-transporting adenosine triphosphatase of rabbit sarcoplasmic reticulum.

A preliminary investigation of the primary structure of the Ca(2+-transporting ATPase (adenosine triphosphatase) protein of rabbit skeletal-muscle sarcoplasmic reticulum is reported. The preparation of derivatives of delipidated protein in a form suitable for sequence analysis is described. Tryptic peptides containing S-carboxymethylcysteine residues were isolated from the reduced carboxymethylated protein, and their sequences were partially determined. The results are consistent with mol.wt. about 105000 for the polypeptide, and the absence of extended repeated lengths of sequence. The distribution of tryptophan and cysteine residues between large, aggregated peptides and soluble tryptic peptides shows that these residues are concentrated in different regions of the primary structure. This observation agrees with other evidence that these residues are, on the whole, widely separated in the native protein. The details of the procedures used to isolate the peptides, and the evidence for the determination of their sequences, are given Supplementary Publication SUP 50085 (30 pages), which has been deposited at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem.J. (1978) 169, 5.

Adenosine Triphosphatases↗