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Biomedical subjects

T Williams

Publications and source records attributed to T Williams.

At least 217 records · Page 12Linked to original sources

Cardiopulmonary transplantation service establishment in the 1990s: Australia--a developing country?

1. A National Transplantation Service has been established at the Alfred Hospital performing more than 50 transplants per year. 2. Increased access to transplantation technology has facilitated an improvement in national population servicing from 2.7 to 6.2 transplants per million population per year. National funding of A$4.062 million per year has been secured. 3. Basic research into organ preservation has facilitated transcontinental organ procurement. 4. An active lung transplantation program has been established synchronous with the cardiac transplant service activities. 5. MCS program establishment has paralleled clinical transplantation activities. 6. Budget management and cost containment has been achieved through rationalisation of management protocols.

Australia↗

Sequence specific protein binding to and activation of the TGF-beta 3 promoter through a repeated TCCC motif.

We have previously characterized the TGF-beta 3 promoter and shown that the activity of this promoter is highly variable in different cell types. Although the promoter contains a proximal cAMP responsive element, which is critical to basal and forskolin-induced promoter activity, this element is not responsible for the variable, cell-specific regulation of the promoter. In this paper, we identify a 25 base pair sequence in the proximal region of the TGF-beta 3 promoter that binds a novel DNA-binding protein. This region includes the sequence T-CCCTCCCTCCC, (3 x TCCC), and mutation of these T-CCC repeats inhibits protein binding. Further, we show that in the cell line A375, which we have previously shown expresses high levels of TGF-beta 3 mRNA, this region is responsible for mediating high level TGF-beta 3 promoter activity. Immediately 3' to the 3 x TCCC sequence is a consensus AP-2 binding site, however, we show that this region does not bind AP-2, and AP-2 does not transactivate the TGF-beta 3 promoter. Therefore, we provide strong evidence that high level expression of TGF-beta 3 in A375 cells results from transactivation of the TGF-beta 3 promoter by a protein that binds to a repeated TCCC motif in the promoter and suggest that this DNA-binding protein likely also regulates aspects of developmental and tissue-specific expression of this cytokine.

Animals↗

Characterization of a dimerization motif in AP-2 and its function in heterologous DNA-binding proteins.

The mammalian transcription factor AP-2 is a retinoic acid inducible sequence-specific DNA-binding protein that is developmentally regulated. In this report, the functional domains necessary for AP-2 DNA binding were studied. AP-2 required a dimerization domain and an adjacent region of net basic charge to achieve a sequence-specific protein:DNA interaction. The sequences responsible for dimerization consisted of two putative amphipathic alpha helices separated by a large intervening span region. This helix-span-helix (HSH) domain was unable to bind DNA when separated from the basic region, but was still capable of dimerization. The ability of the HSH domain to function as a module that promotes DNA binding through dimerization was further demonstrated by attaching it to the heterologous basic region of the c-Jun proto-oncogene product. The resulting chimeric protein specifically recognized an AP-1 DNA-binding site in the absence of an intact c-Jun leucine repeat and in a manner that was dependent on the presence of a functional AP-2 dimerization domain.

Adenosine Triphosphate↗

Bacterial resistances to mercury and copper.

Heavy metals are toxic to living organisms. Some have no known beneficial biological function, while others have essential roles in physiological reactions. Mechanisms which deal with heavy metal stress must protect against the deleterious effects of heavy metals, yet avoid depleting the cell of a heavy metal which is also an essential nutrient. We describe the mechanisms of resistance in Escherichia coli to two different heavy metals, mercury and copper. Resistance of E. coli to mercury is reasonably well understood and is known to occur by transport of mercuric ions into the cytoplasmic compartment of the bacterial cell and subsequent reductive detoxification of mercuric ions. Recent mutational analysis has started to uncover the mechanistic detail of the mercuric ion transport processes, and has shown the essential nature of cysteine residues in transport of Hg(II). Resistance to copper is much less well understood, but is known to involve the increased export of copper from the bacterial cell and modification of the copper; the details of the process are still being elucidated. Expression of both metal resistance determinants is regulated by the corresponding cation. In each case the response enables the maintenance of cellular homeostasis for the metal. The conclusions drawn allow us to make testable predictions about the regulation of expression of resistance to other heavy metals.

Amino Acid Sequence↗

Self-report measures of obsessionality, depression and social anxiety in a school population of adolescents.

The results are reported for a non-clinical school population of 252 adolescent subjects, aged 13 to 15 years, responding to the Maudsley Obsessive-Compulsive Inventory (MOCI), the Children's Depression Inventory (CDI) and the List of Social Situation Problems (LSSP). The scales intercorrelated significantly but appear to measure different aspects of self perception. No significant age or gender effects emerged in any. The results obtained are compared with those of previous studies and the use of the MOCI in adolescent populations discussed.

Adolescent↗

Determining cancer-patient-management educational needs.

The authors have proposed a model for curriculum planning and continuing medical education (CME) program development (JCE 4:255-259, 1989.) This paper reports the results of an application of this model. The knowledge examination administered was developed by specialists and family practice physicians, covering four cancer sites and eight cancer-patient management stages. The purpose of this application was to evaluate the model regarding its effectiveness in terms of whether specific core competencies could be identified as the basis for curriculum planning and/or CME program-planning use. It was assumed that data from this assessment could be extrapolated from the residency context to the development of CME programs. A total of 200 respondent reports (interns, residents, faculty) from 15 institutions (medical schools or hospitals) were analyzed. In general, more education improves test scores; faculty (6.5% of the respondents) averaged about 66% correct answers. The highest percentage of correct responses was associated with the site Breast (60%) and the stage Shared Care (70%). The lowest percentage of correct values was associated with the site Colorectal (45%) and the stage Treatment (44%). The pair Colorectal/Treatment produced the lowest percentage of correct answers observed (27%). The proactive model applied in this study was successful regarding determination of core-competency deficiencies. Participant responses were useful for identifying cancer-patient-management core-competency deficiencies, knowledge gaps that could be used for both curriculum planning and CME program development. Residency directors from participating institutions have reported using this information to modify the educational experience of individual residents as well as to modify their cancer program curriculum.(ABSTRACT TRUNCATED AT 250 WORDS)

Curriculum↗

Risks and benefits of laparoscopic cholecystectomy in the community hospital setting.

Laparoscopic cholecystectomy has rapidly become more popular than open cholecystectomy. To further evaluate the safety and efficacy of laparoscopic cholecystectomy in the community setting, the first 190 patients to undergo the procedure in Saginaw, Michigan were studied. There were 159 females and 31 males. The mean age was 47.8 years. All patients had symptoms consistent with biliary tract disease and most had gallstones proven by preoperative ultrasound. The mean operative time was 84 minutes but decreased from 161 minutes the first month of the study to 74 minutes by the seventh month. Eighty-seven percent of patients were tolerating a regular diet by postoperative day 1. Ninety-six percent of patients were requiring only oral pain medications by postoperative day 1. Seventy percent of patients were discharged by postoperative day one while 91% were discharged by postoperative day 2. Six patients were converted to open cholecystectomy due to acute inflammation, significant bleeding or extensive adhesions. There were no deaths and the morbidity rate was 9.5%. The most significant complication was postoperative bile leak which occurred in two patients. Patients returned to work a mean of 16.1 days following surgery and to their normal daily activities at home a mean of 12.9 days postoperatively. This study of the first 190 laparoscopic cholecystectomies in Saginaw affirms the safety and feasibility of this procedure in the community setting in selected patients.

Biliary Tract Diseases↗

Effect of acupuncture-point stimulation on diastolic blood pressure in hypertensive subjects: a preliminary study.

Electrical stimulation of four specific acupuncture points (Liver 3, Stomach 36, Large Intestine 11, and the Groove for Lowering Blood Pressure) was examined in order to determine the effect of this stimulation on diastolic blood pressure in 10 subjects with diastolic hypertension. Subjects were randomly divided into two groups: (1) an Acu-ES group, which received electrical stimulation applied to the four antihypertensive acupuncture points, and (2) a Sham-ES group, which received electrical stimulation applied to non-acupuncture-point areas. A repeated-measures analysis of variance revealed a significant, immediate poststimulation reduction of diastolic blood pressure for the Acu-Es group versus the Sham-ES group. Further studies are needed to determine whether there are other acupuncture points, stimulation characteristics, or modalities that can enhance this treatment effect and whether the treatment effect can last for a clinically significant period of time.

Acupuncture Points↗

Analysis of the DNA-binding and activation properties of the human transcription factor AP-2.

The mammalian transcription factor AP-2 is a sequence-specific DNA-binding protein expressed in neural crest lineages and regulated by retinoic acid. Here we report a structure/function analysis of the DNA-binding and transcription activation properties of the AP-2 protein. DNA contact studies indicate that AP-2 binds as a dimer to a palindromic recognition sequence. Furthermore, cross-linking and immunoprecipitation data illustrate that AP-2 exists as a dimer even in the absence of DNA. Examination of cDNA mutants reveals that the sequences responsible for DNA binding are located in the carboxy-terminal half of the protein. In addition, a domain mediating dimerization forms an integral component of this DNA-binding structure. Expression of AP-2 in mammalian cells demonstrates that transcriptional activation requires an additional amino-terminal domain that contains an unusually high concentration of proline residues. This proline-rich activation domain also functions when attached to the heterologous DNA-binding region of the GAL4 protein. This study reveals that although AP-2 shares an underlying modular organization with other transcription factors, the regions of AP-2 involved in transcriptional activation and DNA binding/dimerization have novel sequence characteristics.

Amino Acid Sequence↗

Dual chamber pacing aborts vasovagal syncope induced by head-up 60 degrees tilt.

To determine if pacing might prevent syncope in cardioinhibitory 'Malignant Vasovagal Syndrome' (also known as 'Neurally-Mediated Bradycardia/Hypotension'), a study of dual chamber pacing during head-up 60 degrees tilt was undertaken. Paired invasive tilts were performed in 10 patients who had a history of recurrent syncope, normal routine investigations including electrophysiological study and prior tilt-induced vasovagal syncope. Vasovagal reactions of identical severity were produced by prolonged 60 degrees head-up tilt on consecutive days in seven out of 10 patients. On day 2, without pacing, seven patients had tilt-induced vasovagal reactions and six became syncopal during the reaction. On day 3, with temporary DVI pacing with rate hysteresis, seven patients had tilt-induced vasovagal reactions and 1 patient was syncopal. Syncope was aborted in the other five patients. DVI pacing significantly improved cardiac index (CI) (one +/- 0.2 to 1.6 +/- 0.3 L/min/m2, P less than 0.01) and mean arterial blood pressure (MABP) (30 +/- 11 to 48 +/- 12 mmHg, P less than 0.01) during vasovagal reactions on day 3 compared with day 2. The mean period of time that patients could tolerate in the tilted position after the onset of the tilt-induced vasovagal reaction was significantly prolonged by pacing from 0.9 +/- 1.2 to 3.2 +/- 1.6 min (P less than 0.01). Dual chamber pacing may abort syncope in 85% of patients with cardioinhibitory malignant vasovagal syndrome. Pacing may prolong consciousness sufficiently during a vasovagal reaction to allow injury to be avoided.

Adult↗

Pseudoaneurysm of the popliteal artery as a complication of an osteochondroma. A review of the literature and a case report.

False aneurysm of the femoral artery was associated with a solitary osteochondroma of the femur in a 22-year-old man. An extensive review of the literature and the problems related to diagnosis revealed that the aneurysm was apparently unique. Contrary to previous reports, computed tomography and angiography did not establish the diagnosis. The physical findings were more informative.

Adult↗

Human versus animal insulin in the management of insulin-dependent diabetes: lack of effect on fetal growth.

It is generally accepted that the human placenta is impermeable to free insulin and that insulin present in the fetus is entirely of fetal origin. A recent study suggested that antibody-bound animal insulin crosses the placental barrier and may exert direct effects on fetal growth. We hypothesized that mothers with insulin-dependent diabetes treated with animal insulin would have infants with higher birth weights and ponderal indices compared with mothers treated with human insulin. We studied 209 mothers with insulin-dependent diabetes who were enrolled in our program and who delivered after 28 weeks' gestation: 170 were treated with animal insulin and 39 with human insulin. There were no differences between the groups in the mean birth weight (adjusted by gestational age at delivery) or ponderal index of the infants. The rate of macrosomia (birth weight greater than the 90th percentile for gestational age or ponderal index above 2.85) was similar in both groups. The sample size was adequate to yield a power of 80% to detect a difference between groups of 179 g or more in birth weight and 0.1 g/cm3 in ponderal index. We suggest that the type of insulin (animal versus human) used by the pregnant insulin-dependent diabetic mother has no bearing on fetal weight gain.

Adult↗

A functional classification of respiratory compromise in spinal cord injury.

Spinal cord injury (SCI) patients have unique care needs, particularly related to the respiratory system. Respiratory problems now comprise a major cause of death in the acute and chronic phases of SCI, especially among quadriplegics. Previous literature has analyzed respiratory muscle dysfunction in SCI according to neurologic levels of injury (Alvarez, Peterson & Lunsford, 1981; McMichan, Michel & Westbrook, 1980). In general, the higher the level of injury, the greater the respiratory compromise and need for ventilatory assistance. Although level of injury is significant, it cannot be used as the sole determinant of respiratory compromise. For example, a 25 year old C4 quadriplegic with an intact diaphragm might have less respiratory impairment than a 60 year old C6 quadriplegic with CHF and a history of COPD. A new classification of SCI patients according to amount of respiratory compromise was developed by our team at the Spinal Cord Injury Unit at the Palo Alto VA Medical Center. The patient is scored in three categories: 1) level of injury; 2) completeness of injury; and 3) associating factors, i.e. age, preinjury chronic lung disease. The purpose of this grouping is to better predict the amount of ventilatory impairment in SCI patients. Used during the initial assessment, patients at high risk for impairment could be determined and optimal respiratory care initiated. This classification can also be used as a clinical nursing tool. Using this scoring system, the nurse could anticipate the patient's respiratory needs, i.e. suctioning, chest physiotherapy, oxygen, hydration, nutritional support and teaching of patient and family in order to comprehensively plan and implement care.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Right and left ventricular performance after single and double lung transplantation. The Toronto Lung Transplant Group.

Twelve single lung and nine double lung transplant recipients were studied before transplantation and at 3 months and 1 year after transplantation with serial right and left ventricular radionuclide angiograms. The resting right ventricular ejection fraction increased in the double lung recipients from 31% +/- 5% before transplantation to 43% +/- 11% at 3 months after transplantation (p less than 0.05) and then remained stable to 1 year. The single lung recipients also demonstrated a significant rise in ejection fraction from 25% +/- 11% before transplantation to 36% +/- 12% at 3 months after transplantation. Again, this remained stable to 1 year. The exercise right ventricular ejection fraction also showed a significant posttransplantation rise in the double lung recipients (p less than 0.005) that remained stable to 1 year. In the single lung recipients a trend was seen for a rise in the exercise right ventricular ejection fraction that did not reach statistical significance by 1 year after transplantation. Neither group had a significant change in rest or exercise left ventricular ejection fraction. The systemic blood pressure increased significantly by 1 year after transplantation in both groups. The heart rate increase with exercise at 3 months after transplantation was significantly greater in the single lung group (42 +/- 13 beats/min) than in the double lung group (14 +/- 13 beats/min) (p less than 0.005). These data indicate that a significant improvement in right ventricular function occurs after single and double lung transplantation.

Adult↗

Refractive state, ocular anatomy, and accommodative range of the sea otter (Enhydra lutris).

Sea otters are carnivorous, amphibious mammals that are active both above and under water. Accordingly, it might be expected that their eyes are adapted for both aerial and aqueous vision. We examined the anatomy and physiological optics of the sea otter eye with a view towards describing and explaining its amphibious visual characteristics. We employed photokeratoscopy to measure the refractive power of the sea otter cornea, which we found to be 59 D. Using video dynamic photorefraction, we found that sea otters can focus targets clearly both in air and water, relying on accommodation to compensate for the refractive loss of their corneas upon immersion in water. Our anatomical investigations revealed that the anterior epithelium of the cornea is extensively developed, as is the iris musculature, meridional ciliary muscle, and the corneoscleral venous plexus. The first feature is most likely an adaptation to the salinity of the marine environment. We believe the latter features are part of a novel, well-developed lenticular accommodative mechanism.

Accommodation, Ocular↗

Detection of verotoxin in stool specimens.

A total of 132 fecal specimens containing verotoxin (VT) were subjected to counter-current immunoelectrophoresis (CIE). Of these, 113 (85.6%) were found to be positive by CIE. Another 71 stool specimens containing E. coli serogroup O157 but with flagellar antigens other than H7 were tested for verotoxin by CIE. These stool specimens were negative for VT on Vero cell monolayers. Of these 71 stool specimens, 6 (8.5%) gave positive tests for verotoxin by CIE. Forty stool specimen filtrates which were negative for VT (negative controls) were also subjected to CIE. One of these stool specimen filtrates gave a line of precipitation by CIE. The specificity of the CIE test was 93.7%, and the sensitivity was 85.6%. False-positive results may have been due to an antibody component against the somatic antigen (O157) in the antitoxin used; this is a limitation of the CIE test. In a related evaluation, 302 stool specimen filtrates containing VT were retested with Vero cell suspension cultures in microdilution plates. Of these, 281 stool specimen filtrates showed cytotoxic effects within 24 h, while the remaining 21 filtrates showed the effects within 48 h. The use of Vero cell suspension culture is as reliable as the use of Vero cell monolayers and provides detection of verotoxin 24 to 48 h sooner.

Animals↗