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Biomedical subjects

J Allen

Publications and source records attributed to J Allen.

At least 19 recordsLinked to original sources
PubMed1992

Incomplete process of recombinant human platelet-derived growth factor produced in yeast and its effect on the biological activity.

Partially purified recombinant human Platelet-derived Growth Factor BB homodimer isolated from yeast culture media contains variable amounts of unprocessed PDGF-BB. This unprocessed PDGF-BB is found as a result of incomplete cleavage of the precursor to form the mature protein. Although the signal peptide is efficiently removed, a fraction of the PDGF secreted has an extended sequence corresponding to the truncated yeast alpha-factor leader. The data suggest that it is the amino acid chain from the truncated a-factor leader and not the sugar moiety attached to it that is responsible for the higher mitogenic activity found in this unprocessed molecule compared to highly purified PDGF-BB.

Amino Acid Sequence↗
PubMed1992

Choroid plexus carcinoma--responses to chemotherapy alone in newly diagnosed young children.

Choroid plexus carcinoma (CPC) arising in the infant poses several treatment dilemmas. The tumor is often not totally resectable at presentation given its large size and tendency to invade adjacent brain. Because of its predisposition to regrow and metastasize, some form of postoperative cytotoxic therapy is required. Chemotherapy (CHT), as opposed to radiotherapy (RT), has a more desirable risk/benefit role in infants, since it is relatively sparing of late neurologic sequelae. Three young male children presented with large intraventricular CPC at 9, 18, and 27 months of age. One child had subarachnoid metastases at diagnosis and the other two had localized disease. Subtotal resections were accomplished and all three required VP shunts. Initial CHT consisted of four monthly courses of cisplatin (20 mg/m2) and etoposide (100 mg/m2), both administered intravenously, daily, for five days. After four courses, two children had complete responses and one had stable disease. Additional CHT was given but one child developed a local recurrence and another diffuse CNS metastases. Both died with intratumoral hemorrhages at 5 and 57 months following diagnosis. The third child remains in continuous remission 46 months after diagnosis. None of the children received RT. Chemotherapy may permit long term deferral of RT. More aggressive CHT regimens should be explored in infants with CPC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Development of a digital adaptive control system for PO2 regulation in a membrane oxygenator.

Regulation of gas exchange in artificial lungs (oxygenators) during cardiopulmonary bypass is normally achieved by manual control of the gas composition and flow in response to intermittent sampling of the arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2). Manual control often results in abnormal blood gases which have been implicated in patient morbidity as well as influencing perfusion safety. Fine control of PaO2 and PaCO2 may be achieved by a combination of an in-line blood gas monitoring system and a membrane type oxygenator which is automatically regulated. The overall dynamics of the oxygenation process and control system components are complex and have nonlinear, multivariable and time-varying characteristics. Consequently, an adaptive control system approach is necessary. The implementation of a digital self-tuning control regime for PaO2 is described here. The controller is based on an explicit Linear Quadratic Gaussian (LQG) self-tuning control design which is presented using a polynomial equation approach. The controller performance was investigated in in vitro experiments. The self-tuner performed satisfactorily with various sensor/oxygenator combinations for blood flow and temperature load disturbances. In contrast, a nonadaptive (proportional-integral, PI) type of control system was found to be unsuitable.

Carbon Dioxide↗
PubMed1992

Dupuytren's and epilepsy revisited.

The incidence of Dupuytren's disease amongst the residents of two epileptic centres was found to be 12.0% in one and 38.1% in the other. The overall incidence at the second was significantly higher than a control population (16.0%) and this difference was particularly apparent in patients over 50 years old. The distribution of the Dupuytren's disease was found to be very similar to that of non-epileptic patients. At both centres, the disease process was more severe, with an increased incidence of contractures. Drug therapy was not clearly implicated in the aetiology of this condition.

Adult↗
PubMed1992

Methodological concerns in evaluating psychiatric nursing care modalities and a proposed standard group protocol format for nurse-led groups.

The importance of detailing therapeutic effort and its outcome cannot be underestimated. The need to document outcomes has been re-emphasized in recent psychiatric mental health literature; however, the methodology for addressing threats to validity is well established. This article identifies the problems and issues related to a systematic evaluation of a therapeutic group intervention in an inpatient setting, specifically threats to validity, and describes the processes used in planning and implementing a standard group protocol format. The findings of this project depicting problems in the clarity and precision of documenting nursing practice are believed to be typical and generalizable. However, problems related to clarity and precision have not been addressed in the nursing literature. For a number of reasons, nursing staff members have not been sensitized to the importance of describing their practices in sufficient detail to allow others to replicate these practices. And yet, adequate evaluations of nursing efforts, particularly programmatic initiatives, require systematic testing with repeated trials. Although no description can describe in absolute terms what occurred, clear and precise descriptions of an intervention provide the foundation for valid conclusions about the effort. A detailed standard group protocol format provides a basis for establishing internal validity in subsequent quasi-experimental research designs as well as program evaluation studies.

Hospitalization↗
PubMed1992

Nonoperative management of major blunt renal trauma in children: in-hospital morbidity and long-term followup.

The management of 26 children with major renal injury secondary to blunt trauma was reviewed. Emergency computerized tomography (CT) was performed in all instances. Injury ranged from parenchymal laceration to vascular avulsion. Early surgical exploration was done in 5 children due to hemodynamic instability, renal pedicle injury or suspected malignancy. The remaining 21 children were observed. Of these children 5 had associated intra-abdominal organ injuries. The average length of hospitalization was 13.4 days and the average intensive care unit stay was 6.9 days. A third of the children were transfused with an average 10.8 cc/kg. of packed red cells. Ten patients (47.6%) had febrile episodes that lasted an average of 3 days. No foci of infection other than bladder urine were identified and there were no infected perirenal collections. In 2 children ureteral stents were placed cystoscopically. Exploration was performed in 1 child for delayed hemorrhage 2 months after hospital discharge. Followup CT was available in 15 patients and all kidneys functioned, including 3 with residual focal scarring, 2 with parenchymal calcifications and 1 with a cyst. Eleven patients were evaluated clinically at least 1 year after injury and all were asymptomatic, while 1 child had mild diastolic hypertension. In conclusion, nonoperative management results in an excellent long-term outcome in the majority of cases. In-hospital morbidity is minimal and early surgical exploration should be reserved for those with hemodynamic instability or renal pedicle injury. Immediate CT is an invaluable aid in categorizing and managing these patients.

Adolescent↗
PubMed1992

Hypermnesia using auditory input.

The author investigated whether hypermnesia would occur with auditory input. In addition, the author examined the effects of subjects' knowledge that they would later be asked to recall the stimuli. Two groups of 26 subjects each were given three successive recall trials after they listened to an audiotape of 59 high-imagery nouns. The subjects in the uninformed group were not told that they would later be asked to remember the words; those in the informed group were. Hypermnesia was evident, but only in the uninformed group.

Acoustic Stimulation↗
PubMed1992

Effects of thiopentone and chlormethiazole on human myometrial arteries from term pregnant women.

We have investigated the effects of thiopentone and chlormethiazole on maternal intramyometrial arteries dissected from myometrial biopsies taken during Caesarean section at term. Ring preparations were mounted in organ baths and isometric tension was recorded. Thiopentone 10(-4)-10(-3) mol litre-1 inhibited responses to K+ depolarization, noradrenaline and vasopressin. Chlormethiazole 3 x 10(-5)-3 x 10(-3) mol litre-1 inhibited responses to noradrenaline, while a concentration of 3 x 10(-3) mol litre-1 was required to attenuate responses to vasopressin and K+ depolarization. Neither of the two agents affected relaxant responses to prostacyclin. The results did not yield evidence that clinical use of thiopentone and chlormethiazole should impair uteroplacental vascular perfusion by a direct effect.

Arginine Vasopressin↗
PubMed1992

Deficient nifedipine oxidation: a rare inherited trait associated with cystic fibrosis kindreds.

Previous studies have indicated that there is weak genetic linkage between the defective gene in cystic fibrosis (CFTR) and the gene encoding the nifedipine metabolizing enzyme P4503A4 which are both located on chromosome 7. To examine further this possible association, nifedipine metabolism was investigated in a group of 59 volunteers, and 17 adult cystic fibrosis patients and 37 of their relatives. In agreement with the majority of previous studies, the volunteer group showed a unimodal distribution of recoveries for the major metabolite M-II ranging from 33 to 78% excretion in 8 h. In the case of both the cystic fibrosis patients and their parents, the distribution of recoveries was shifted to the left with five out of 20 parents and three out of 11 unrelated cystic fibrosis patients showing recoveries below the range observed in the volunteer group. This poor metabolism appeared to be both reproducible and heritable and did not appear to be a consequence of mutations in the CFTR gene.

Adolescent↗
PubMed1992

The distribution of alpha 6 beta 4 integrins in lesional and non-lesional skin in bullous pemphigoid.

The alpha 6 beta 4 integrin is associated ultrastructurally with the hemidesmosomes of the basal keratinocytes and with the bullous pemphigoid antigen (BPA), suggesting an important role in adhesion of epidermal cells to the basement membrane. Using an immunofluorescence technique with chain-specific monoclonal antibodies to the alpha and beta subunits we have investigated the distribution of the alpha 6 beta 4 integrin in normal skin (n = 3) and in BP skin (uninvolved, perilesional and lesional) [n = 11]). The findings have been compared with other types of subepidermal blisters and with normal skin split by chemical means (n = 2) and by suction (n = 2). The distribution of alpha 6 beta 4 integrin was compared with that of bullous pemphigoid antigen (BPA) and with other basement membrane zone (BMZ) macromolecules, laminin, collagen type IV, collagen type VII and the BM600 antigen. In uninvolved, perilesional and early pre-blistered lesional BP skin the distribution of both the alpha 6 and beta 4 integrin subunits, BPA laminin, collagen types IV and VII and the BM600 antigen was identical to normal skin, i.e. a linear band in the BMZ. Within BP blisters, both alpha 6 and beta 4 integrin subunits and BPA were absent, except in two blisters in which the integrin expression was retained in the blister roof, despite loss of BPA. The other BMZ components were expressed on the blister floor.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Beta 141 Leu is not deleted in the unstable haemoglobin Atlanta-Coventry but is replaced by a novel amino acid of mass 129 daltons.

Reinvestigation of the structure of the beta-chain of Hb Atlanta-Coventry (beta 75 Leu----Pro, beta 141 Leu deleted) confirmed the presence of two abnormalities; however, analysis of the aberrant beta Co14 tryptic peptide by liquid secondary ion mass spectrometry indicated that the beta 141 Leu (mass 113 daltons) was not deleted but replaced by a novel amino acid of mass 129 daltons. The new amino acid in peptide beta Co14 was uncharged at pH 6.5, more hydrophillic than leucine and susceptible to cleavage by both chymotrypsin and carboxypeptidase A. We propose that the new residue is likely to be hydroxyleucine and that it results from post-translational oxidation of beta 141 Leu as a consequence of perturbation of the haem environment caused by the beta 75 Leu----Pro mutation in the E helix (E19). This proposal is entirely consistent with recent DNA analysis which showed that beta At-Co was not the product of a third beta-globin gene and that neither of the two beta-globin genes, beta A nor beta Atlanta, contained a deletion of the beta 141 Leu codon. We have subsequently found this modified amino acid at position beta 141 in two other unstable haemoglobins, both of which involve mutations on the haem side of the E helix.

Amino Acid Sequence↗
PubMed1992

A comparison of external rate responsive pacemakers with identical implanted units.

Seven patients with previously implanted accelerometer-based DDDR pacemakers had an identically programmed external pacemaker taped onto their chest. Both units underwent a simultaneous test to set the sensitivity of the accelerometer. The units were then programmed to record the pacing rates for a 15-minute period. The patients underwent an exercise course that included walking and stairs. After the exercise, the patients sat for 3 minutes and the pacing rates from the test were telemetered. The pacing rate was compared at 2 minutes, 4 minutes, peak, and 3 minutes postexercise. The mean standard deviation (SED) for the external pacemaker was 97.9 at 3.53 ppm, 102 at 10.6 ppm, 106 at 8.94 ppm, and 71.3 at 2.29 ppm at 2, 4, peak, and decay, respectively. The mean SED for the implanted pacemaker was 98.1 at 5.76 ppm, 100 at 10.2 ppm, 104 8.24 ppm, 72.4 at 2.88 ppm at 2, 4, peak, and decay, respectively. Difference between pacemakers in ppm was 0.286, 2.0, 2.71, and 1.14 at 2, 4, peak, and decay, respectively. A 95% confidence interval in ppm was -5.28 to 5.85, -10.1 to 14.1, -7.30 to 12.7, and -1.89 to 4.17 at 2, 4, peak, and decay, respectively. In all patients there was a high confidence correlation between the implanted and external unit. An external unit can be used to predict the rate response of an accelerometer-based pacemaker without any adjustments to the pacing parameters.

Acceleration↗
PubMed1992

The gene encoding a Prevotella loescheii lectin-like adhesin contains an interrupted sequence which causes a frameshift.

We cloned and sequenced the Prevotella loescheii gene plaA, which encodes a lectin-like adhesin that mediates the coaggregation of P. loescheii 1295 with Streptococcus oralis 34. A probe derived from the N-terminal amino acid sequence of the purified adhesin was used to identify the plaA gene from a P. loescheii genomic library constructed in lambda GEM-11. Sequence analysis of plaA indicates that the initial translation product contains a 22-amino-acid leader. The reading frame of the plaA gene is interrupted after amino acid 28 of the mature protein by a TAA termination codon. Amplification of the P. loescheii genomic DNA in the region surrounding this codon by the polymerase chain reaction followed by DNA sequencing of the cloned DNA fragment established that this stop codon was not an experimental artifact. A frameshift beginning 29 bp downstream of the ochre terminator was required to access the only large open reading frame in the gene. Amino acid sequences of six purified peptides derived by limited proteolysis of adhesin with endoproteinase Lys-C matched the downstream amino acid sequence derived by translation of the large open reading frame. The gene coding sequence of 2.4 kb contains sufficient information for the synthesis of an 89-kDa protein. A putative rho-independent terminator (delta G = -25.5 kcal/mol [ca. -107 kJ/mol]) was detected 38 bp downstream from the plaA stop codon.

Adhesins, Bacterial↗
PubMed1992

Continuity equation and Gorlin formula compared with directly observed orifice area in native and prosthetic aortic valves.

Orifice areas calculated by the continuity and Gorlin equations have been shown to correlate well in vivo. The continuity equation, however, gives underestimates compared with the Gorlin formula and it is not clear which is the more accurate. Both equations have therefore been tested against maximal orifice area measured by planimetry in eight prepared native aortic valves and four bioprostheses. A computer controlled, ventricular flow simulator (cycled at 70 beats/min) was used at five different stroke volumes that gave cardiac outputs of 2.8 to 7.0 l/min. The mean difference between measured and estimated orifice area was zero for the continuity equation, but -0.14 cm2 for the conventional Gorlin formula. Thus the Gorlin formula tended to give overestimates compared with both measured area and area estimated by the continuity equation, probably because of the effect of pressure recovery. When predictive equations derived from these data were tested, residual standard deviations were around 0.3 cm2 at all stroke volumes for the continuity equation, around 0.2 cm2 for the invasive Gorlin formula, and between 0.2 and 0.4 cm2 for the modified Gorlin formula. These results suggest that estimates of orifice area in an individual valve as judged by any of the equations tested should be seen as a guide to rather than as a precise measure of actual orific area.

Anthropometry↗
PubMed1992

Can autism be detected at 18 months? The needle, the haystack, and the CHAT.

Autism is currently detected only at about three years of age. This study aimed to establish if detection of autism was possible at 18 months of age. We screened 41 18-month-old toddlers who were at high genetic risk for developing autism, and 50 randomly selected 18-month-olds, using a new instrument, the CHAT, administered by GPs or health visitors. More than 80% of the randomly selected 18-month-old toddlers passed on all items, and none failed on more than one of pretend play, protodeclarative pointing, joint-attention, social interest, and social play. Four children in the high-risk group failed on two or more of these five key types of behaviour. At follow-up at 30 months of age, the 87 children who had passed four or more of these key types of behaviour at 18 months of age had continued to develop normally. The four toddlers who had failed on two or more of these key types of behaviour at 18 months received a diagnosis of autism by 30 months.

Age Factors↗