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Biomedical subjects

M Ward

Publications and source records attributed to M Ward.

At least 235 records · Page 13Linked to original sources
PubMed1990

Improved production of chymosin in Aspergillus by expression as a glucoamylase-chymosin fusion.

We have extended the work on chymosin production in Aspergillus by constructing an expression vector in which the cDNA encoding bovine prochymosin B was fused in frame immediately following the codon for the last amino acid of the A. awamori glucoamylase (glaA) gene. Transformation of A. awamori with this plasmid led to the secretion of considerably higher amounts of chymosin than obtained with previous chymosin expression vectors. We present evidence that mature chymosin is autocatalytically released from the glucoamylase-chymosin fusion protein after secretion.

Amino Acid Sequence↗
PubMed1990

Efficient gene transfer in live mice using a unique retroviral packaging line.

Irradiated mice were transplanted with cells containing a foreign gene to evaluate gene transfer and expression as a model for gene therapy. Using a uniquely safe and efficient retroviral packaging line developed in this laboratory (GP + E86), we demonstrate efficient and safe long-term transfer of the neomycin resistance (neoR) gene into mice. By infusing cells obtained from spleen colonies of primary post-transplant mice marked with the neoR gene into irradiated recipients, secondary and tertiary generations of recipient mice were produced. There was very low reconstitution activity of single stem cells in these successive generations of mice. We conclude that many more than one stem cell is necessary for successful long-term bone marrow transplantation in mice, presumably as a result of the relatively low frequency of stem cell cycling.

Animals↗
PubMed1990

Retroviral gene transfer using safe and efficient packaging cell lines.

One of the requirements for the use of retroviral vectors in human gene therapy is a packaging cell line which is incapable of producing replication-competent virus and which produces high titers of replication-deficient vector virus. Wild-type virus may be produced through recombinational events between the helper virus and a retroviral vector. We have constructed an ecotropic packaging cell line, GP + E-86, and an amphotropic packaging cell line, GP + envAm12, in which the viral gag and pol genes are on one plasmid and the viral env gene is on another plasmid. Both plasmids contain deletions of the packaging sequence and the 3' LTR. The fragmented helper virus genomes, when introduced into 3T3 cells, produce titers of retrovirus which are comparable to the titers produced from packaging cells containing the helper virus genome on a single plasmid. We have found no evidence for the generation of wild-type retrovirus using the GP + E-86 and GP + envAm12 packaging lines, either alone or in combination with the N2 retroviral vector. We also show that these packaging cell lines can be used to transfer the neoR gene of the N2 vector into mouse hematopoietic cells, followed by successful (48-52%), long-term (up to 200 days) transplantation into irradiated recipients. These results indicate that these packaging lines are safe and efficient for use in experiments designed for murine (using GP + E-86) and human (using GP + envAm12) gene therapy.

Animals↗
PubMed1990

Chest wall motion and expiratory muscle use during phonation in normal humans.

The pattern of rib cage (RC) and abdomen (AB) motion and the electromyograms of the triangularis sterni (TS) and abdominal external oblique (EO) muscles were studied during speech and reading in six normal uninformed subjects in the sitting posture. Most phrases were started from within the tidal breathing range and extended below RC and AB spontaneous end-expiratory volumes. On the average, 75% of the change in chest wall volume occurred below the resting end-expiratory level. The expired volume resulted from a large predominance of RC displacement, and this was accompanied by marked recruitment of the TS. The EO was also generally activated, but the pattern of activation was less consistent. We conclude that 1) speech occurs primarily below the spontaneous end-expiratory level; 2) most of the volume change is caused by active emptying of the RC produced, at least in part, by contraction of the TS; 3) concomitant activation of the abdominal muscles serves to optimize the inspiratory function of the diaphragm, which has to contract rapidly between phrases to refill the respiratory system.

Adult↗
PubMed1990

A preliminary study of unresolved grief in families of seriously mentally ill patients.

Investigations of the grief reactions experienced by families when a relative develops a serious mental illness have been hampered by the lack of an appropriate instrument to measure such reactions. The authors devised the Mental Illness Version of the Texas Inventory of Grief, adapted from the Texas Revised Inventory of Grief, to assess family members' initial and present feelings about their relative's loss of mental health. A test of the instrument with 58 family members of patients with schizophrenia or bipolar disorder revealed a surprisingly low level of initial grief but higher levels of present grief.

Adaptation, Psychological↗
PubMed1990

Discriminant attitudes and beliefs about condoms in young, multi-partner heterosexuals.

Four hundred and eight people aged 15-35 years who reported having more than one sexual partner of the opposite sex in the past year or who thought it likely that they would do so in the next year were surveyed about their sexual behaviour, concern about acquired immunodeficiency syndrome and sexually transmitted diseases and attitudes to condom use. Differences in concerns and attitudes between regular and non- or irregular condom users and between men and women are reported. Three conceptually coherent factors (condom use as positive action; condom use as cue to embarrassment; and condom use as antithetical to good sex) discriminated between users and non-users. Implications for health promotion campaigns designed to promote condom use are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Measuring and interpreting organizational culture.

Organizational culture is an abstract, yet potent managerial concept. With roots in several disciplines, several perspectives and definitions of organizational culture have emerged. One perspective focuses on norms and expectations within the organization. In this article, the authors present a quantitative approach to measuring and interpreting organizational culture based on established norms and expected behavior.

Humans↗
PubMed1990

Persisting inapparent chlamydial infection in a trachoma endemic community in The Gambia.

In a Gambian village with endemic trachoma, C. trachomatis was isolated from some 50% of children with active trachoma but from only 1% of adults with scarring sequelae. One possibility is that individuals with progressive scarring disease have clinically inapparent, non-productive infection which cannot be detected by cell culture. In whole village survey, 12% of 808 people carried ocular chlamydial antigen detected by EIA. Around 70% of antigen positive children were clinically active. By contrast, for adults age greater than 25 years, only 10% of antigen positives were clinically active. Antigen positive adults were twice as likely to develop scarring disease and longitudinal studies suggest that they are intermittently infectious. Implications for the pathology and prevention of trachoma are discussed.

Adolescent↗
PubMed1990

Irritable bowel syndrome.

The irritable bowel syndrome is characterised by symptoms of apparent gastrointestinal origin, in the absence of any demonstrable structural abnormality. The author emphasises the need for the exclusion of organic disease and outlines the minimum investigations required to achieve this.

Clinical Protocols↗
PubMed1990

Rehospitalization after initial rehabilitation for acute spinal cord injury: incidence and risk factors.

Many acute spinal cord injury (SCI) patients require rehospitalization after discharge from initial rehabilitation. Previous studies of rehospitalization for these patients have been cross-sectional with respect to time since injury (in years), and have not allowed for comparison of patients with equal exposure to the risk of medical complications once they have reentered the community. To examine the incidence, cause, and monetary cost of rehospitalizations during the first year after discharge from initial rehabilitative care (day 365), the medical records of 88 consecutive, acute SCI patients who completed initial rehabilitation at a regional model SCI care system were reviewed. Cases were excluded from the study if the patient was lost to follow-up before day 365. All readmissions to the regional SCI care system during the follow-up period were reviewed for primary diagnosis, length of stay (LOS), and hospital charges incurred. Thirty-four patients (39%) were readmitted at least once by day 365. There was a total of 47 readmissions; mean LOS was 11.9 +/- 2.1 days per admission (+/- 1SE), and mean hospital charge per admission was $9,683. Univariate comparisons between the characteristics of patients who were readmitted vs those who were not indicated that the readmitted group was less educated (11.8 +/- 2.1 years vs 12.9 +/- 0.3 years, p less than 0.05) and had a substantially longer initial rehabilitation LOS (88.9 +/- 6.6 days vs 72.9 +/- 5.1 days, p less than 0.05). Readmissions were less common among patients who were discharged at Frankel class C or D (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Protein C activity levels in endotoxin-induced disseminated intravascular coagulation in a dog model.

The levels of protein C (PC) and other coagulation factors were monitored during endotoxin-induced disseminated intravascular coagulation (DIC) in the dog. Initial evaluation of the effectiveness of intradermal administration of bolus endotoxin quantities into the dog, demonstrated induction of DIC in the canine, without the severe side effects associated with bacterial sepsis. Quantitative determination of canine plasma protein C levels were performed using a multiple step amidolytic assay, that included a specific precipitation of the vitamin K-dependent proteins from citrated plasma, followed by thrombin activation (and neutralization) and subsequent measurement of the activated protein C (APC) by chromogen hydrolysis. This investigation demonstrated, that over a twenty-four hour interval, intradermal administration of endotoxin produces a gradual decrease in the PC activity levels, concomitant with a significant reduction in the Factor V, Factor VIII and fibrinogen levels and platelet count, and a prolongation of the Prothrombin Time and Partial Thromboplastin Time. During the first 6 hours, protein C levels fell below the pre-levels and remained significantly lower in the surviving dogs. Thus, this endotoxin-induced DIC animal model permits evaluation of various hemostatic parameters, yet diminishes the severe clinical findings associated with DIC.

Animals↗
PubMed1989

Oesophageal ruptures and perforations--a review.

Oesophageal ruptures or tears carry a high mortality if they are not recognized and if therapy is delayed. This is so particularly for cases of spontaneous rupture of the oesophagus which carry a higher mortality and morbidity than do cases of iatrogenic injuries. With the widespread use of fibreoptic oesophagogastroscopy, which has been accompanied by the therapeutic manipulation of strictures and tumours, the number of iatrogenic perforations has increased substantially. We report our experience with 23 oesophageal perforations or ruptures that were seen over a 15-year period. The results of both the surgical and the conservative management of such lesions were excellent and were based on the clinical condition of the patient and on the extent of the extravasation of contrast media. Our results show that not all cases of oesophageal perforations require immediate surgical exploration and that the results of surgical treatment are excellent if the diagnosis is made early.

Adolescent↗
PubMed1989

Relationship of dental caries and fluorosis to fluoride supplement history in a non-fluoridated sample of schoolchildren.

A random sample of 206 Michigan children, aged from 9 to 13, were examined for fluorosis from a larger group of 2038 children participating in a dental project. Clinical examinations included caries data (DMFS) and assessment of fluorosis by use of the Tooth Surface Index of Fluorosis (TSIF). Separate examiners were used for each index. The response rate of a questionnaire mailed to parents to gather information on residence histories, use of fluoride supplements, and antibiotics was 78%. The prevalence of fluorosis was about 20% among the respondents. Of the 4868 tooth surfaces examined, 9.2% were affected by fluorosis. In all cases, dental fluorosis was judged as mild, with most occurrences on the posterior teeth. No instances of moderate or severe fluorosis were found. The caries experience of respondents was 1.69 +/- 2.73 DMFS. Caries experience does not appear to be significantly related to income, education, or fluoride supplement use. Approximately 52% of respondents were reported to have taken fluoride supplements with various degrees of consistency. Parents' education was positively related to both prevalence of fluorosis (odds ratio = 2.2) and use of fluoride supplements (odds ratio = 2.7). No significant relation was revealed with evidence of fluorosis and use of supplements. This study shows a relatively mild level of dental fluorosis in a sample of children from a non-fluoridated area. Dental fluorosis in this group does not appear to be related to use of fluoride supplements or differences in caries experience.

Adolescent↗
PubMed1989

Seizures in haemodialysis patients treated with recombinant human erythropoietin.

Administration of recombinant erythropoietin (r-HuEPO) is an effective treatment for the anaemia of chronic renal failure, but in some patients it has been accompanied by elevated blood pressure. This study focuses on seven patients with end-stage renal failure, managed on haemodialysis, who developed probable hypertensive encephalopathy with seizures during treatment with r-HuEPO. All made a full recovery. The events were not clearly related to the haemoglobin concentrations achieved, and four patients have subsequently been restarted on r-HuEPO therapy at a reduced dose, resulting in a slower increase in haemoglobin with no recurrence of episodes of severe hypertension. Close attention needs to be paid to blood pressure in patients commencing erythropoietin therapy, and it seems prudent to aim for a gradual increase in haemoglobin concentration to allow the circulation to adapt to changes in oxygen delivery and haematocrit.

Adult↗
PubMed1989

Early postoperative endoscopic sphincterotomy for retained common duct stones.

The results of endoscopic sphincterotomy in 30 patients with retained common bile duct stones and a T-tube in situ following surgical exploration of the common bile duct are presented. Successful stone extraction was achieved in 27 cases (90%). There was one death, which was not procedure related. Early postoperative T-tube cholangiography is advocated and if necessary sphincterotomy can be safely performed 1 week following surgery. This approach has advantages in shortening hospital stay and minimising patient discomfort.

Adult↗